Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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9 pages, 1034 KiB  
Article
Innovation in Actinic Keratosis Assessment: Artificial Intelligence-Based Approach to LC-OCT PRO Score Evaluation
by Fabia Daxenberger, Maximilian Deußing, Quirine Eijkenboom, Charlotte Gust, Janis Thamm, Daniela Hartmann, Lars E. French, Julia Welzel, Sandra Schuh and Elke C. Sattler
Cancers 2023, 15(18), 4457; https://doi.org/10.3390/cancers15184457 - 7 Sep 2023
Cited by 9 | Viewed by 1452
Abstract
Actinic keratosis (AK) is a common skin cancer in situ that can progress to invasive SCC. Line-field confocal optical coherence tomography (LC-OCT) has emerged as a non-invasive imaging technique that can aid in diagnosis. Recently, machine-learning algorithms have been developed that can automatically [...] Read more.
Actinic keratosis (AK) is a common skin cancer in situ that can progress to invasive SCC. Line-field confocal optical coherence tomography (LC-OCT) has emerged as a non-invasive imaging technique that can aid in diagnosis. Recently, machine-learning algorithms have been developed that can automatically assess the PRO score of AKs based on the dermo-epidermal junction’s (DEJ’s) protrusion on LC-OCT images. A dataset of 19.898 LC-OCT images from 80 histologically confirmed AK lesions was used to test the performance of a previous validated artificial intelligence (AI)-based LC-OCT assessment algorithm. AI-based PRO score assessment was compared to the imaging experts’ visual score. Additionally, undulation of the DEJ, the number of protrusions detected within the image, and the maximum depth of the protrusions were computed. Our results show that AI-automated PRO grading is highly comparable to the visual score, with an agreement of 71.3% for the lesions evaluated. Furthermore, this AI-based assessment was significantly faster than the regular visual PRO score assessment. The results confirm our previous findings of the pilot study in a larger cohort that the AI-based grading of LC-OCT images is a reliable and fast tool to optimize the efficiency of visual PRO score grading. This technology has the potential to improve the accuracy and speed of AK diagnosis and may lead to better clinical outcomes for patients. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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15 pages, 1938 KiB  
Review
Sex Differences in the Efficacy of Immune Checkpoint Inhibitors in Neoadjuvant Therapy of Non-Small Cell Lung Cancer: A Meta-Analysis
by Guillermo Suay, Juan-Carlos Garcia-Cañaveras, Francisco Aparisi, Agustin Lahoz and Oscar Juan-Vidal
Cancers 2023, 15(18), 4433; https://doi.org/10.3390/cancers15184433 - 6 Sep 2023
Cited by 7 | Viewed by 1986
Abstract
Non-small cell lung cancer (NSCLC) is one of the world’s leading causes of morbidity and mortality. ICIs alone or combined with chemotherapy have become the standard first-line treatment of metastatic NSCLC. The impressive results obtained have stimulated our interest in applying these therapies [...] Read more.
Non-small cell lung cancer (NSCLC) is one of the world’s leading causes of morbidity and mortality. ICIs alone or combined with chemotherapy have become the standard first-line treatment of metastatic NSCLC. The impressive results obtained have stimulated our interest in applying these therapies in early disease stage treatments, as neoadjuvant immunotherapy has shown promising results. Among many of the factors that may influence responses, the role played by sex is attracting increased interest and needs to be addressed. Here, we aim to first review the state of the art regarding neoadjuvant ICIs, whether they are administered in monotherapy or in combination with chemotherapy at stages IB-IIIA, particularly at stage IIIA, before analyzing whether sex may influence responses. To this end, a meta-analysis of publicly available data comparing male and female major pathological responses (MPR) and pathological complete responses (pCR) was performed. In our meta-analysis, MPR was found to be significantly higher in females than in males, with an odds ratio (OR) of 1.82 (95% CI 1.13–2.93; p = 0.01), while pCR showed a trend to be more favorable in females than in males, but the OR of 1.62 was not statistically significant (95% CI 0.97–2.75; p = 0.08). Overall, our results showed that sex should be systematically considered in future clinical trials settings in order to establish the optimal treatment sequence. Full article
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20 pages, 1599 KiB  
Review
The Influence of the Microbiome on Immunotherapy for Gastroesophageal Cancer
by Neda Dadgar, Vinay Edlukudige Keshava, Moses S. Raj and Patrick L. Wagner
Cancers 2023, 15(18), 4426; https://doi.org/10.3390/cancers15184426 - 5 Sep 2023
Cited by 3 | Viewed by 1945
Abstract
Immunotherapy has shown promise as a treatment option for gastroesophageal cancer, but its effectiveness is limited in many patients due to the immunosuppressive tumor microenvironment (TME) commonly found in gastrointestinal tumors. This paper explores the impact of the microbiome on the TME and [...] Read more.
Immunotherapy has shown promise as a treatment option for gastroesophageal cancer, but its effectiveness is limited in many patients due to the immunosuppressive tumor microenvironment (TME) commonly found in gastrointestinal tumors. This paper explores the impact of the microbiome on the TME and immunotherapy outcomes in gastroesophageal cancer. The microbiome, comprising microorganisms within the gastrointestinal tract, as well as within malignant tissue, plays a crucial role in modulating immune responses and tumor development. Dysbiosis and reduced microbial diversity are associated with poor response rates and treatment resistance, while specific microbial profiles correlate with improved outcomes. Understanding the complex interactions between the microbiome, tumor biology, and immunotherapy is crucial for developing targeted interventions. Microbiome-based biomarkers may enable personalized treatment approaches and prediction of patient response. Interventions targeting the microbiome, such as microbiota-based therapeutics and dietary modifications, offer the potential for reshaping the gut microbiota and creating a favorable TME that enhances immunotherapy efficacy. Further research is needed to reveal the underlying mechanisms, and large-scale clinical trials will be required to validate the efficacy of microbiome-targeted interventions. Full article
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19 pages, 356 KiB  
Review
Radiomics: The New Promise for Differentiating Progression, Recurrence, Pseudoprogression, and Radionecrosis in Glioma and Glioblastoma Multiforme
by Mohammadreza Alizadeh, Nima Broomand Lomer, Mobin Azami, Mohammad Khalafi, Parnian Shobeiri, Melika Arab Bafrani and Houman Sotoudeh
Cancers 2023, 15(18), 4429; https://doi.org/10.3390/cancers15184429 - 5 Sep 2023
Cited by 3 | Viewed by 2639
Abstract
Glioma and glioblastoma multiform (GBM) remain among the most debilitating and life-threatening brain tumors. Despite advances in diagnosing approaches, patient follow-up after treatment (surgery and chemoradiation) is still challenging for differentiation between tumor progression/recurrence, pseudoprogression, and radionecrosis. Radiomics emerges as a promising tool [...] Read more.
Glioma and glioblastoma multiform (GBM) remain among the most debilitating and life-threatening brain tumors. Despite advances in diagnosing approaches, patient follow-up after treatment (surgery and chemoradiation) is still challenging for differentiation between tumor progression/recurrence, pseudoprogression, and radionecrosis. Radiomics emerges as a promising tool in initial diagnosis, grading, and survival prediction in patients with glioma and can help differentiate these post-treatment scenarios. Preliminary published studies are promising about the role of radiomics in post-treatment glioma/GBM. However, this field faces significant challenges, including a lack of evidence-based solid data, scattering publication, heterogeneity of studies, and small sample sizes. The present review explores radiomics’s capabilities in following patients with glioma/GBM status post-treatment and to differentiate tumor progression, recurrence, pseudoprogression, and radionecrosis. Full article
(This article belongs to the Special Issue The Current Status of Brain Tumors Imaging)
14 pages, 286 KiB  
Article
Changes in the Number of Gastrointestinal Cancers and Stage at Diagnosis with COVID-19 Pandemic in Japan: A Multicenter Cohort Study
by Kento Kuzuu, Noboru Misawa, Keiichi Ashikari, Shigeki Tamura, Shingo Kato, Kunihiro Hosono, Masato Yoneda, Takashi Nonaka, Shozo Matsushima, Tatsuji Komatsu, Atsushi Nakajima and Takuma Higurashi
Cancers 2023, 15(17), 4410; https://doi.org/10.3390/cancers15174410 - 4 Sep 2023
Cited by 7 | Viewed by 1750
Abstract
This retrospective cohort study compared the number of newly diagnosed patients, stage at diagnosis, and detection process of gastrointestinal cancers based on hospital-based cancer registry data at two tertiary Japanese hospitals. The pre-COVID-19 period was from January 2017 to February 2020, with phase [...] Read more.
This retrospective cohort study compared the number of newly diagnosed patients, stage at diagnosis, and detection process of gastrointestinal cancers based on hospital-based cancer registry data at two tertiary Japanese hospitals. The pre-COVID-19 period was from January 2017 to February 2020, with phase 1 (midst of COVID-19 pandemic) from March to December 2020 and phase 2 (the transition period to the “new normal”) from January to December 2021. Each month, the number of patients diagnosed with esophageal, gastric, colorectal, pancreatic, liver, and biliary tract cancers were aggregated, classified by stage and detection process, and compared, including a total of 6453 patients. The number of colorectal Stage 0-II patients decreased significantly in phase 1 and increased in phase 2. The total number of colorectal cancer patients returned to pre-COVID-19 levels (mean monthly patients [SD]: 41.61 [6.81] vs. 36.00 [6.72] vs. 46.00 [11.32]). The number of patients with gastric cancer Stage I significantly decreased in phase 2 following phase 1. The number of gastric cancer patients decreased significantly from pre-COVID-19 levels (30.63 [6.62] vs. 22.40 [5.85] vs. 24.50 [4.15]). During phase 2, the number of patients diagnosed after screening with colorectal cancer increased significantly, whereas that with gastric cancer remained considerably lower. The number of Stage III colorectal and gastric cancer patients increased significantly from the pre-COVID-19 levels. Thus, gastric cancer may not be optimally screened during phases 1 and 2. There was a significant increase in patients with Stage III colorectal and gastric cancers from the pre-COVID-19 period; hence, the stage at diagnosis may have progressed. Full article
(This article belongs to the Collection The Impact of COVID-19 Infection in Cancer)
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17 pages, 3895 KiB  
Article
Unlocking the Power of Benchmarking: Real-World-Time Data Analysis for Enhanced Sarcoma Patient Outcomes
by Bruno Fuchs, Georg Schelling, Maria Elyes, Gabriela Studer, Beata Bode-Lesniewska, Mario F. Scaglioni, Pietro Giovanoli, Philip Heesen and on behalf of the SwissSarcomaNetwork
Cancers 2023, 15(17), 4395; https://doi.org/10.3390/cancers15174395 - 2 Sep 2023
Cited by 10 | Viewed by 2433
Abstract
Benchmarking is crucial for healthcare providers to enhance quality and efficiency, notably for complex conditions like sarcomas. Multidisciplinary teams/sarcoma boards (MDT/SBs) are vital in sarcoma management, but differences in their processes can affect patient outcomes and treatment costs, despite adherence to international guidelines. [...] Read more.
Benchmarking is crucial for healthcare providers to enhance quality and efficiency, notably for complex conditions like sarcomas. Multidisciplinary teams/sarcoma boards (MDT/SBs) are vital in sarcoma management, but differences in their processes can affect patient outcomes and treatment costs, despite adherence to international guidelines. To address this issue, this study aimed to compare two MDT/SBs and establish an interoperable digital platform, Sarconnector®, for real-time-world data assessment and automated analysis. The study included 983 patients, 46.0% of whom female, with a median age of 58 years, and 4.5% of patients presented with metastasis at diagnosis. Differences were observed in the number of first-time presentations, follow-up presentations, primary sarcomas, biopsies and chemotherapy indications between the two MDT/SB. The results highlight the importance of benchmarking and utilizing a harmonized data approach, such as the RWT approach provided by the Sarconnector®, to standardize and evaluate quality and cost metrics. By identifying areas of improvement and making data-driven decisions on the meta-level, healthcare providers can optimize resources and improve patient outcomes. In conclusion, benchmarking with the RWT harmonized data approach provided by the Sarconnector® can help healthcare providers improve the overall effectiveness of the healthcare system and achieve better outcomes for their patients in terms of both outcomes and costs. Full article
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15 pages, 1306 KiB  
Article
Efficacy of Thermal Ablation for Small-Size (0–3 cm) versus Intermediate-Size (3–5 cm) Colorectal Liver Metastases: Results from the Amsterdam Colorectal Liver Met Registry (AmCORE)
by Madelon Dijkstra, Susan van der Lei, Robbert S. Puijk, Hannah H. Schulz, Danielle J. W. Vos, Florentine E. F. Timmer, Hester J. Scheffer, Tineke E. Buffart, M. Petrousjka van den Tol, Birgit I. Lissenberg-Witte, Rutger-Jan Swijnenburg, Kathelijn S. Versteeg and Martijn R. Meijerink
Cancers 2023, 15(17), 4346; https://doi.org/10.3390/cancers15174346 - 31 Aug 2023
Cited by 5 | Viewed by 1968
Abstract
Purpose: Thermal ablation is widely recognized as the standard of care for small-size unresectable colorectal liver metastases (CRLM). For larger CRLM safety, local control and overall efficacy are not well established and insufficiently validated. The purpose of this comparative series was to analyze [...] Read more.
Purpose: Thermal ablation is widely recognized as the standard of care for small-size unresectable colorectal liver metastases (CRLM). For larger CRLM safety, local control and overall efficacy are not well established and insufficiently validated. The purpose of this comparative series was to analyze outcomes for intermediate-size versus small-size CRLM. Material and methods: Patients treated with thermal ablation between December 2000 and November 2021 for small-size and intermediate-size CRLM were included. The primary endpoints were complication rate and local control (LC). Secondary endpoints included local tumor progression-free survival (LTPFS) and overall survival (OS). Results: In total, 59 patients were included in the intermediate-size (3–5 cm) group and 221 in the small-size (0–3 cm) group. Complications were not significantly different between the two groups (p = 0.546). No significant difference between the groups was found in an overall comparison of OS (HR 1.339; 95% CI 0.824–2.176; p = 0.239). LTPFS (HR 3.388; p < 0.001) and LC (HR 3.744; p = 0.004) were superior in the small-size group. Nevertheless, the 1-, 3-, and 5-year LC for intermediate-size CRLM was still 93.9%, 85.4%, and 81.5%, and technical efficacy improved over time. Conclusions: Thermal ablation for intermediate-size unresectable CRLM is safe and induces long-term LC in the vast majority. The results of the COLLISION-XL trial (unresectable colorectal liver metastases: stereotactic body radiotherapy versus microwave ablation—a phase II randomized controlled trial for CRLM 3–5 cm) are required to provide further clarification of the role of local ablative methods for intermediate-size unresectable CRLM. Full article
(This article belongs to the Special Issue Thermal Ablation in the Management for Colorectal Liver Metastases)
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11 pages, 3134 KiB  
Article
Antagonizing MDM2 Overexpression Induced by MDM4 Inhibitor CEP-1347 Effectively Reactivates Wild-Type p53 in Malignant Brain Tumor Cells
by Yuta Mitobe, Shuhei Suzuki, Yurika Nakagawa-Saito, Keita Togashi, Asuka Sugai, Yukihiko Sonoda, Chifumi Kitanaka and Masashi Okada
Cancers 2023, 15(17), 4326; https://doi.org/10.3390/cancers15174326 - 30 Aug 2023
Cited by 4 | Viewed by 2100
Abstract
The development of MDM4 inhibitors as an approach to reactivating p53 in human cancer is attracting increasing attention; however, whether they affect the function of MDM2 and how they interact with MDM2 inhibitors remain unknown. We addressed this question in the present study [...] Read more.
The development of MDM4 inhibitors as an approach to reactivating p53 in human cancer is attracting increasing attention; however, whether they affect the function of MDM2 and how they interact with MDM2 inhibitors remain unknown. We addressed this question in the present study using CEP-1347, an inhibitor of MDM4 protein expression. The effects of CEP-1347, the genetic and/or pharmacological inhibition of MDM2, and their combination on the p53 pathway in malignant brain tumor cell lines expressing wild-type p53 were investigated by RT-PCR and Western blot analyses. The growth inhibitory effects of CEP-1347 alone or in combination with MDM2 on inhibition were examined by dye exclusion and/or colony formation assays. The treatment of malignant brain tumor cell lines with CEP-1347 markedly increased MDM2 protein expression, while blocking CEP-1347-induced MDM2 overexpression by genetic knockdown augmented the effects of CEP-1347 on the p53 pathway and cell growth. Blocking the MDM2–p53 interaction using the small molecule MDM2 inhibitor RG7112, but not MDM2 knockdown, reduced MDM4 expression. Consequently, RG7112 effectively cooperated with CEP-1347 to reduce MDM4 expression, activate the p53 pathway, and inhibit cell growth. The present results suggest the combination of CEP-1347-induced MDM2 overexpression with the selective inhibition of MDM2′s interaction with p53, while preserving its ability to inhibit MDM4 expression, as a novel and rational strategy to effectively reactivate p53 in wild-type p53 cancer cells. Full article
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18 pages, 3065 KiB  
Article
Environmental and Lifestyle Cancer Risk Factors: Shaping Extracellular Vesicle OncomiRs and Paving the Path to Cancer Development
by Valentina Bollati, Paola Monti, Davide Biganzoli, Giuseppe Marano, Chiara Favero, Simona Iodice, Luca Ferrari, Laura Dioni, Francesca Bianchi, Angela Cecilia Pesatori and Elia Mario Biganzoli
Cancers 2023, 15(17), 4317; https://doi.org/10.3390/cancers15174317 - 29 Aug 2023
Cited by 3 | Viewed by 1786
Abstract
Intercellular communication has been transformed by the discovery of extracellular vesicles (EVs) and their cargo, including microRNAs (miRNAs), which play crucial roles in intercellular signaling. These EVs were previously disregarded as cellular debris but are now recognized as vital mediators of biological information [...] Read more.
Intercellular communication has been transformed by the discovery of extracellular vesicles (EVs) and their cargo, including microRNAs (miRNAs), which play crucial roles in intercellular signaling. These EVs were previously disregarded as cellular debris but are now recognized as vital mediators of biological information transfer between cells. Furthermore, they respond not only to internal stimuli but also to environmental and lifestyle factors. Identifying EV-borne oncomiRs, a subset of miRNAs implicated in cancer development, could revolutionize our understanding of how environmental and lifestyle exposures contribute to oncogenesis. To investigate this, we studied the plasma levels of EV-borne oncomiRs in a population of 673 women and 238 men with a body mass index > 25 kg/m2 (SPHERE population). The top fifty oncomiRs associated with the three most common cancers in women (breast, colorectal, and lung carcinomas) and men (lung, prostate, and colorectal carcinomas) were selected from the OncomiR database. Only oncomiRs expressed in more than 20% of the population were considered for statistical analysis. Using a Multivariate Adaptive Regression Splines (MARS) model, we explored the interactions between environmental/lifestyle exposures and EV oncomiRs to develop optimized predictor combinations for each EV oncomiR. This innovative approach allowed us to better understand miRNA regulation in response to multiple environmental and lifestyle influences. By uncovering non-linear relationships among variables, we gained valuable insights into the complexity of miRNA regulatory networks. Ultimately, this research paves the way for comprehensive exposome studies in the future. Full article
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22 pages, 402 KiB  
Review
Recurrent Glioblastoma: A Review of the Treatment Options
by Maria Angeles Vaz-Salgado, María Villamayor, Víctor Albarrán, Víctor Alía, Pilar Sotoca, Jesús Chamorro, Diana Rosero, Ana M. Barrill, Mercedes Martín, Eva Fernandez, José Antonio Gutierrez, Luis Mariano Rojas-Medina and Luis Ley
Cancers 2023, 15(17), 4279; https://doi.org/10.3390/cancers15174279 - 26 Aug 2023
Cited by 17 | Viewed by 6441
Abstract
Glioblastoma is a disease with a poor prognosis. Multiple efforts have been made to improve the long-term outcome, but the 5-year survival rate is still 5–10%. Recurrence of the disease is the usual way of progression. In this situation, there is no standard [...] Read more.
Glioblastoma is a disease with a poor prognosis. Multiple efforts have been made to improve the long-term outcome, but the 5-year survival rate is still 5–10%. Recurrence of the disease is the usual way of progression. In this situation, there is no standard treatment. Different treatment options can be considered. Among them would be reoperation or reirradiation. There are different studies that have assessed the impact on survival and the selection of patients who may benefit most from these strategies. Chemotherapy treatments have also been considered in several studies, mainly with alkylating agents, with data mostly from phase II studies. On the other hand, multiple studies have been carried out with target-directed treatments. Bevacizumab, a monoclonal antibody with anti-angiogenic activity, has demonstrated activity in several studies, and the FDA has approved it for this indication. Several other TKI drugs have been evaluated in this setting, but no clear benefit has been demonstrated. Immunotherapy treatments have been shown to be effective in other types of tumors, and several studies have evaluated their efficacy in this disease, both immune checkpoint inhibitors, oncolytic viruses, and vaccines. This paper reviews data from different studies that have evaluated the efficacy of different forms of relapsed glioblastoma. Full article
12 pages, 2296 KiB  
Review
Proton Therapy in the Adolescent and Young Adult Population
by Safia K. Ahmed and Sameer R. Keole
Cancers 2023, 15(17), 4269; https://doi.org/10.3390/cancers15174269 - 25 Aug 2023
Cited by 2 | Viewed by 2298
Abstract
Background: Adolescent and young adult cancer patients are at high risk of developing radiation-associated side effects after treatment. Proton beam radiation therapy might reduce the risk of these side effects for this population without compromising treatment efficacy. Methods: We review the current literature [...] Read more.
Background: Adolescent and young adult cancer patients are at high risk of developing radiation-associated side effects after treatment. Proton beam radiation therapy might reduce the risk of these side effects for this population without compromising treatment efficacy. Methods: We review the current literature describing the utility of proton beam radiation therapy in the treatment of central nervous system tumors, sarcomas, breast cancer and Hodgkin lymphoma for the adolescent and young adult cancer population. Results: Proton beam radiation therapy has utility for the treatment of certain cancers in the young adult population. Preliminary data suggest reduced radiation dose to normal tissues, which might reduce radiation-associated toxicities. Research is ongoing to further establish the role of proton therapy in this population. Conclusion: This report highlights the potential utility of proton beam radiation for certain adolescent young adult cancers, especially with reducing radiation doses to organs at risk and thereby potentially lowering risks of certain treatment-associated toxicities. Full article
(This article belongs to the Special Issue Proton Therapy Promises and Perils: What Progress Has Been Made?)
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27 pages, 1195 KiB  
Review
Advances in Immunotherapeutics in Pancreatic Ductal Adenocarcinoma
by Tarak Chouari, Francesca Soraya La Costa, Nabeel Merali, Maria-Danae Jessel, Shivan Sivakumar, Nicola Annels and Adam E. Frampton
Cancers 2023, 15(17), 4265; https://doi.org/10.3390/cancers15174265 - 25 Aug 2023
Cited by 11 | Viewed by 3182
Abstract
Pancreatic ductal adenocarcinoma (PDAC) accounts for up to 95% of all pancreatic cancer cases and is the seventh-leading cause of cancer death. Poor prognosis is a result of late presentation, a lack of screening tests and the fact some patients develop resistance to [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) accounts for up to 95% of all pancreatic cancer cases and is the seventh-leading cause of cancer death. Poor prognosis is a result of late presentation, a lack of screening tests and the fact some patients develop resistance to chemotherapy and radiotherapy. Novel therapies like immunotherapeutics have been of recent interest in pancreatic cancer. However, this field remains in its infancy with much to unravel. Immunotherapy and other targeted therapies have yet to yield significant progress in treating PDAC, primarily due to our limited understanding of the disease immune mechanisms and its intricate interactions with the tumour microenvironment (TME). In this review we provide an overview of current novel immunotherapies which have been studied in the field of pancreatic cancer. We discuss their mechanisms, evidence available in pancreatic cancer as well as the limitations of such therapies. We showcase the potential role of combining novel therapies in PDAC, postulate their potential clinical implications and the hurdles associated with their use in PDAC. Therapies discussed with include programmed death checkpoint inhibitors, Cytotoxic T-lymphocyte-associated protein 4, Chimeric Antigen Receptor-T cell therapy, oncolytic viral therapy and vaccine therapies including KRAS vaccines, Telomerase vaccines, Gastrin Vaccines, Survivin-targeting vaccines, Heat-shock protein (HSP) peptide complex-based vaccines, MUC-1 targeting vaccines, Listeria based vaccines and Dendritic cell-based vaccines. Full article
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29 pages, 4688 KiB  
Article
Brain Tumor Detection Based on Deep Learning Approaches and Magnetic Resonance Imaging
by Akmalbek Bobomirzaevich Abdusalomov, Mukhriddin Mukhiddinov and Taeg Keun Whangbo
Cancers 2023, 15(16), 4172; https://doi.org/10.3390/cancers15164172 - 18 Aug 2023
Cited by 66 | Viewed by 8190
Abstract
The rapid development of abnormal brain cells that characterizes a brain tumor is a major health risk for adults since it can cause severe impairment of organ function and even death. These tumors come in a wide variety of sizes, textures, and locations. [...] Read more.
The rapid development of abnormal brain cells that characterizes a brain tumor is a major health risk for adults since it can cause severe impairment of organ function and even death. These tumors come in a wide variety of sizes, textures, and locations. When trying to locate cancerous tumors, magnetic resonance imaging (MRI) is a crucial tool. However, detecting brain tumors manually is a difficult and time-consuming activity that might lead to inaccuracies. In order to solve this, we provide a refined You Only Look Once version 7 (YOLOv7) model for the accurate detection of meningioma, glioma, and pituitary gland tumors within an improved detection of brain tumors system. The visual representation of the MRI scans is enhanced by the use of image enhancement methods that apply different filters to the original pictures. To further improve the training of our proposed model, we apply data augmentation techniques to the openly accessible brain tumor dataset. The curated data include a wide variety of cases, such as 2548 images of gliomas, 2658 images of pituitary, 2582 images of meningioma, and 2500 images of non-tumors. We included the Convolutional Block Attention Module (CBAM) attention mechanism into YOLOv7 to further enhance its feature extraction capabilities, allowing for better emphasis on salient regions linked with brain malignancies. To further improve the model’s sensitivity, we have added a Spatial Pyramid Pooling Fast+ (SPPF+) layer to the network’s core infrastructure. YOLOv7 now includes decoupled heads, which allow it to efficiently glean useful insights from a wide variety of data. In addition, a Bi-directional Feature Pyramid Network (BiFPN) is used to speed up multi-scale feature fusion and to better collect features associated with tumors. The outcomes verify the efficiency of our suggested method, which achieves a higher overall accuracy in tumor detection than previous state-of-the-art models. As a result, this framework has a lot of potential as a helpful decision-making tool for experts in the field of diagnosing brain tumors. Full article
(This article belongs to the Special Issue Brain Tumor: Recent Advances and Challenges)
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26 pages, 5728 KiB  
Article
Proteomic Mapping of the Interactome of KRAS Mutants Identifies New Features of RAS Signalling Networks and the Mechanism of Action of Sotorasib
by Aoife Nolan, Cinzia Raso, Walter Kolch, Alex von Kriegsheim, Kieran Wynne and David Matallanas
Cancers 2023, 15(16), 4141; https://doi.org/10.3390/cancers15164141 - 17 Aug 2023
Cited by 2 | Viewed by 4058
Abstract
RAS proteins are key regulators of cell signalling and control different cell functions including cell proliferation, differentiation, and cell death. Point mutations in the genes of this family are common, particularly in KRAS. These mutations were thought to cause the constitutive activation [...] Read more.
RAS proteins are key regulators of cell signalling and control different cell functions including cell proliferation, differentiation, and cell death. Point mutations in the genes of this family are common, particularly in KRAS. These mutations were thought to cause the constitutive activation of KRAS, but recent findings showed that some mutants can cycle between active and inactive states. This observation, together with the development of covalent KRASG12C inhibitors, has led to the arrival of KRAS inhibitors in the clinic. However, most patients develop resistance to these targeted therapies, and we lack effective treatments for other KRAS mutants. To accelerate the development of RAS targeting therapies, we need to fully characterise the molecular mechanisms governing KRAS signalling networks and determine what differentiates the signalling downstream of the KRAS mutants. Here we have used affinity purification mass-spectrometry proteomics to characterise the interactome of KRAS wild-type and three KRAS mutants. Bioinformatic analysis associated with experimental validation allows us to map the signalling network mediated by the different KRAS proteins. Using this approach, we characterised how the interactome of KRAS wild-type and mutants is regulated by the clinically approved KRASG12C inhibitor Sotorasib. In addition, we identified novel crosstalks between KRAS and its effector pathways including the AKT and JAK-STAT signalling modules. Full article
(This article belongs to the Special Issue RAS Signaling Pathway in Cancer Therapy)
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8 pages, 1477 KiB  
Article
Metastases of OSCC Based on Oral Lichen Ruber Planus
by Katharina Theresa Obermeier, Sabina Noreen Wuersching, Paris Liokatis, Wenko Smolka, Philipp Poxleitner, Christin Kleye, Michael Ehrenfeld, Maximilian Kollmuss and Sven Otto
Cancers 2023, 15(16), 4092; https://doi.org/10.3390/cancers15164092 - 14 Aug 2023
Cited by 3 | Viewed by 1336
Abstract
Oral lichen ruber planus (OLP) is a poorly understood chronically inflammatory disease of the oral mucosa. Malignant transformation into oral squamous cell carcinoma (OSCC) is reported in between 1–2% of cases in the literature. After malignant transformation, surgical treatment—meaning tumor resection combined with [...] Read more.
Oral lichen ruber planus (OLP) is a poorly understood chronically inflammatory disease of the oral mucosa. Malignant transformation into oral squamous cell carcinoma (OSCC) is reported in between 1–2% of cases in the literature. After malignant transformation, surgical treatment—meaning tumor resection combined with neck dissection—is recommended. The recommended extent of treatment is controversial in the literature because this kind of OSCC is often a highly differentiated tumor with a lower risk for lymph nodal spreading. This study aims to overview 103 patients treated in our department due to OLP. The primary outcome parameter was the development of metastases in OLP patients compared to a group of OSCC patients without OLP and the comparison of survival in between both groups. Statistical analysis showed a significantly lower risk for patients with OSCC and with OLP for lymph nodal spreading (p = 0.013). Patients with OSCC and without OLP had a 4.76-higher risk for lymph nodal spreading. On the other hand, second metachronous tumor occurred more often in patients with OSCC and OLP. Overall, OSCC based on OLP occurs more often in female patients, is more highly differentiated and comes with a lower risk for metastases but has a higher risk for second metachronous tumors. Therefore, special attention should be paid to patients with OSCC based on OLP when planning adjuvant therapy and clinical follow-up. The indication for postoperative radiation should be made cautiously in this case, and clinical controls should be performed more closely due to the risk of recurrent disease or tumors at different locations. Full article
(This article belongs to the Collection Advances in Diagnostics and Treatment of Head and Neck Cancer)
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13 pages, 653 KiB  
Article
Elevated Glycated Haemoglobin (HbA1c) Is Associated with an Increased Risk of Pancreatic Ductal Adenocarcinoma: A UK Biobank Cohort Study
by Declan McDonnell, Adrian W. E. Cheang, Sam Wilding, Sarah H. Wild, Adam E. Frampton, Christopher D. Byrne and Zaed Z. Hamady
Cancers 2023, 15(16), 4078; https://doi.org/10.3390/cancers15164078 - 13 Aug 2023
Cited by 3 | Viewed by 1817
Abstract
Background: The role of dysglycaemia as a risk marker for Pancreatic Ductal Adenocarcinoma (PDAC) is uncertain. We investigated the relationship between glycated haemoglobin (HbA1c) and incident PDAC using a retrospective cohort study within the UK Biobank. Methods: A study involving 499,804 participants from [...] Read more.
Background: The role of dysglycaemia as a risk marker for Pancreatic Ductal Adenocarcinoma (PDAC) is uncertain. We investigated the relationship between glycated haemoglobin (HbA1c) and incident PDAC using a retrospective cohort study within the UK Biobank. Methods: A study involving 499,804 participants from the UK Biobank study was undertaken. Participants were stratified by diabetes mellitus (DM) status, and then by HbA1c values < 42 mmol/mol, 42–47 mmol/mol, or ≥48 mmol/mol. Cox proportional hazard models were used to describe the association between HbA1c category (with time-varying interactions) and incident PDAC. Results: PDAC occurred in 1157 participants during 11.6 (10.9–12.3) years follow up [(median (interquartile range)]. In subjects without known DM at baseline, 12 months after recruitment, the adjusted hazard ratios (aHR, 95% CI) for incident PDAC for HbA1c 42–47 mmol/mol compared to HbA1c < 42 mmol/mol (reference group) was 2.10 (1.31–3.37, p = 0.002); and was 8.55 (4.58–15.99, p < 0.001) for HbA1c ≥ 48 mmol/mol. The association between baseline HbA1c and incident PDAC attenuated with increasing duration of time of follow-up to PDAC diagnosis. Conclusions: Dysglycaemia detected by elevated HbA1c is associated with an increased risk of PDAC. The strength of the association between elevated HbA1c and incident PDAC is inversely proportional to the time from detecting dysglycaemia but remains significant for at least 60 months following HbA1c testing. Full article
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13 pages, 1034 KiB  
Article
Real-World Evidence on the Clinical Characteristics and Management of Patients with Chronic Lymphocytic Leukemia in Spain Using Natural Language Processing: The SRealCLL Study
by Javier Loscertales, Pau Abrisqueta-Costa, Antonio Gutierrez, José Ángel Hernández-Rivas, Rafael Andreu-Lapiedra, Alba Mora, Carolina Leiva-Farré, María Dolores López-Roda, Ángel Callejo-Mellén, Esther Álvarez-García and José Antonio García-Marco
Cancers 2023, 15(16), 4047; https://doi.org/10.3390/cancers15164047 - 10 Aug 2023
Cited by 2 | Viewed by 3213
Abstract
The SRealCLL study aimed to obtain real-world evidence on the clinical characteristics and treatment patterns of patients with chronic lymphocytic leukemia (CLL) using natural language processing (NLP). Electronic health records (EHRs) from seven Spanish hospitals (January 2016–December 2018) were analyzed using EHRead® [...] Read more.
The SRealCLL study aimed to obtain real-world evidence on the clinical characteristics and treatment patterns of patients with chronic lymphocytic leukemia (CLL) using natural language processing (NLP). Electronic health records (EHRs) from seven Spanish hospitals (January 2016–December 2018) were analyzed using EHRead® technology, based on NLP and machine learning. A total of 534 CLL patients were assessed. No treatment was detected in 270 (50.6%) patients (watch-and-wait, W&W). First-line (1L) treatment was identified in 230 (43.1%) patients and relapsed/refractory (2L) treatment was identified in 58 (10.9%). The median age ranged from 71 to 75 years, with a uniform male predominance (54.8–63.8%). The main comorbidities included hypertension (W&W: 35.6%; 1L: 38.3%; 2L: 39.7%), diabetes mellitus (W&W: 24.4%; 1L: 24.3%; 2L: 31%), cardiac arrhythmia (W&W: 16.7%; 1L: 17.8%; 2L: 17.2%), heart failure (W&W 16.3%, 1L 17.4%, 2L 17.2%), and dyslipidemia (W&W: 13.7%; 1L: 18.7%; 2L: 19.0%). The most common antineoplastic treatment was ibrutinib in 1L (64.8%) and 2L (62.1%), followed by bendamustine + rituximab (12.6%), obinutuzumab + chlorambucil (5.2%), rituximab + chlorambucil (4.8%), and idelalisib + rituximab (3.9%) in 1L and venetoclax (15.5%), idelalisib + rituximab (6.9%), bendamustine + rituximab (3.5%), and venetoclax + rituximab (3.5%) in 2L. This study expands the information available on patients with CLL in Spain, describing the diversity in patient characteristics and therapeutic approaches in clinical practice. Full article
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12 pages, 1157 KiB  
Article
PD-1 Inhibitors in Elderly and Immunocompromised Patients with Advanced or Metastatic Cutaneous Squamous Cell Carcinoma
by Alexander Yakobson, Ashraf Abu Jama, Omar Abu Saleh, Regina Michlin and Walid Shalata
Cancers 2023, 15(16), 4041; https://doi.org/10.3390/cancers15164041 - 10 Aug 2023
Cited by 7 | Viewed by 2499
Abstract
Cutaneous squamous cell carcinoma (cSCC) of the skin is the second most common form of skin cancer, with aging and prolonged exposure to ultraviolet rays being the main causes of the disease. Cemiplimab and pembrolizumab recently gained regulatory approval for the treatment of [...] Read more.
Cutaneous squamous cell carcinoma (cSCC) of the skin is the second most common form of skin cancer, with aging and prolonged exposure to ultraviolet rays being the main causes of the disease. Cemiplimab and pembrolizumab recently gained regulatory approval for the treatment of locally advanced and metastatic cSCC—conditions that are not treatable by surgical resection and/or radiotherapy. Although the results from the clinical trials have been promising, these studies have not included immunosuppressed, elderly patients. In this study, we included all immunocompromised and immunocompetent patients over the age of 75 years diagnosed with locally advanced or metastatic cSCC and treated with cemiplimab or pembrolizumab. The median duration of follow-up from cSCC diagnosis was 35.6 months, 82.9% of patients were male, and the median age was 83 years old. The median progression-free survival was 8.94 months. The incidence of treatment-related adverse events was 85.6%, the majority of which were grades 1 or 2. The disease control rate was 91.4%, the complete response rate was 17.1%, the partial response rate was 51.4%, the stable disease rate was 23%, and the progressive disease rate was 8.7%. Based on this study, cemiplimab and pembrolizumab for the treatment of locally advanced or metastatic cSCC in elderly, immunocompromised patients are efficacious, with acceptable safety profiles. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Therapeutics and Mechanisms)
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15 pages, 945 KiB  
Article
Serum Oxidative and Nitrosative Stress Markers in Clear Cell Renal Cell Carcinoma
by Sabina Galiniak, Marek Biesiadecki, Mateusz Mołoń, Patrycja Olech and Krzysztof Balawender
Cancers 2023, 15(15), 3995; https://doi.org/10.3390/cancers15153995 - 7 Aug 2023
Cited by 3 | Viewed by 1513
Abstract
Oxidative stress is believed to be a factor in the development and progression of renal cell carcinoma (RCC). The identification of the oxidative and nitrosative modification of proteins and the definition of their roles in clear cell RCC (ccRCC) may be helpful in [...] Read more.
Oxidative stress is believed to be a factor in the development and progression of renal cell carcinoma (RCC). The identification of the oxidative and nitrosative modification of proteins and the definition of their roles in clear cell RCC (ccRCC) may be helpful in the elaboration of targeted therapeutic approaches to mitigate protein damage. This study aimed to investigate the status of oxidative/nitrosative stress and to explore its role in the development and progression. The studied group consisted of 48 newly diagnosed ccRCC and 30 healthy controls. Serum levels of oxidative stress markers—advanced oxidation protein products (AOPP), thiol groups, Amadori reaction products, 3-nitrotyrosine, nitrate/nitrite, malondialdehyde (MDA), 4-hydroxy-2-nonenal and total antioxidant capacity (TAC)—were determined. Additionally, associations between tumour stage assessed according to TNM classification, histological grade, and the effect of the presence of angioinvasion on the level of stress markers were evaluated. The levels of Amadori products, 3-nitrotyrosine, and nitrate/nitrite were elevated, while the levels of thiol groups and TAC decreased in the ccRCC group. The levels of AOPP, Amadori, and 3-nitrotyrosine increased, and thiol groups and TAC levels decreased with the increasing pathological stage of the tumour. In the case of advanced histological assessment of the tumour, we found decreasing levels of thiol groups and increasing levels of MDA. In patients with angioinvasion, nitrate/nitrite and MDA levels were significantly elevated compared to those in patients without angioinvasion. Oxidative stress increased with the progression of the disease assessed according to the TNM and histological grade. These results demonstrate systemic oxidative stress in ccRCC, suggesting the therapeutic application of antioxidants. Full article
(This article belongs to the Special Issue Advances in Cancer Glycobiology)
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24 pages, 2108 KiB  
Review
Challenges in Pharmacological Intervention in Perilipins (PLINs) to Modulate Lipid Droplet Dynamics in Obesity and Cancer
by Victória Bombarda-Rocha, Dany Silva, Allal Badr-Eddine, Patrícia Nogueira, Jorge Gonçalves and Paula Fresco
Cancers 2023, 15(15), 4013; https://doi.org/10.3390/cancers15154013 - 7 Aug 2023
Cited by 6 | Viewed by 4128
Abstract
Perilipins (PLINs) are the most abundant proteins in lipid droplets (LD). These LD-associated proteins are responsible for upgrading LD from inert lipid storage structures to fully functional organelles, fundamentally integrated in the lipid metabolism. There are five distinct perilipins (PLIN1–5), each with specific [...] Read more.
Perilipins (PLINs) are the most abundant proteins in lipid droplets (LD). These LD-associated proteins are responsible for upgrading LD from inert lipid storage structures to fully functional organelles, fundamentally integrated in the lipid metabolism. There are five distinct perilipins (PLIN1–5), each with specific expression patterns and metabolic activation, but all capable of regulating the activity of lipases on LD. This plurality creates a complex orchestrated mechanism that is directly related to the healthy balance between lipogenesis and lipolysis. Given the essential role of PLINs in the modulation of the lipid metabolism, these proteins can become interesting targets for the treatment of lipid-associated diseases. Since reprogrammed lipid metabolism is a recognized cancer hallmark, and obesity is a known risk factor for cancer and other comorbidities, the modulation of PLINs could either improve existing treatments or create new opportunities for the treatment of these diseases. Even though PLINs have not been, so far, directly considered for pharmacological interventions, there are many established drugs that can modulate PLINs activity. Therefore, the aim of this study is to assess the involvement of PLINs in diseases related to lipid metabolism dysregulation and whether PLINs can be viewed as potential therapeutic targets for cancer and obesity. Full article
(This article belongs to the Section Cancer Pathophysiology)
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12 pages, 272 KiB  
Review
Neoadjuvant Immunotherapy for Localized Pancreatic Cancer: Challenges and Early Results
by Robert Connor Chick, Andrew J. Gunderson, Shafia Rahman and Jordan M. Cloyd
Cancers 2023, 15(15), 3967; https://doi.org/10.3390/cancers15153967 - 4 Aug 2023
Cited by 6 | Viewed by 2754
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease due to its late presentation and tendency to recur early even after optimal surgical resection. Currently, there are limited options for effective systemic therapy. In addition, PDAC typically generates an immune-suppressive tumor microenvironment; trials [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease due to its late presentation and tendency to recur early even after optimal surgical resection. Currently, there are limited options for effective systemic therapy. In addition, PDAC typically generates an immune-suppressive tumor microenvironment; trials of immunotherapy in metastatic PDAC have yielded disappointing results. There is considerable interest in using immunotherapy approaches in the neoadjuvant setting in order to prime the immune system to detect and prevent micrometastatic disease and recurrence. A scoping review was conducted to identify published and ongoing trials utilizing preoperative immunotherapy. In total, 9 published trials and 27 ongoing trials were identified. The published trials included neoadjuvant immune checkpoint inhibitors, cancer vaccines, and other immune-modulating agents that target mechanisms distinct from that of immune checkpoint inhibition. Most of these are early phase trials which suggest improvements in disease-free and overall survival when combined with standard neoadjuvant therapy. Ongoing trials are exploring various combinations of these agents with each other and with chemotherapy and/or radiation. Rational combination immunotherapy in addition to standard neoadjuvant therapy has the potential to improve outcomes in PDAC, but further clinical trials are needed, particularly those which utilize an adaptive trial design. Full article
(This article belongs to the Special Issue Neoadjuvant Therapy of Pancreatic Cancer)
16 pages, 1657 KiB  
Systematic Review
Methylated Circulating Tumor DNA in Blood as a Tool for Diagnosing Lung Cancer: A Systematic Review and Meta-Analysis
by Morten Borg, Sara Witting Christensen Wen, Rikke Fredslund Andersen, Signe Timm, Torben Frøstrup Hansen and Ole Hilberg
Cancers 2023, 15(15), 3959; https://doi.org/10.3390/cancers15153959 - 3 Aug 2023
Cited by 8 | Viewed by 2320
Abstract
Lung cancer is the leading cause of cancer-related deaths, and early detection is crucial for improving patient outcomes. Current screening methods using computed tomography have limitations, prompting interest in non-invasive diagnostic tools such as methylated circulating tumor DNA (ctDNA). The PRISMA guidelines for [...] Read more.
Lung cancer is the leading cause of cancer-related deaths, and early detection is crucial for improving patient outcomes. Current screening methods using computed tomography have limitations, prompting interest in non-invasive diagnostic tools such as methylated circulating tumor DNA (ctDNA). The PRISMA guidelines for systematic reviews were followed. The electronic databases MEDLINE, Embase, Web of Science, and Cochrane Library were systematically searched for articles. The search string contained three main topics: Lung cancer, blood, and methylated ctDNA. The extraction of data and quality assessment were carried out independently by the reviewers. In total, 33 studies were eligible for inclusion in this systematic review and meta-analysis. The most frequently studied genes were SHOX2, RASSF1A, and APC. The sensitivity and specificity of methylated ctDNA varied across studies, with a summary sensitivity estimate of 46.9% and a summary specificity estimate of 92.9%. The area under the hierarchical summary receiver operating characteristics curve was 0.81. The included studies were generally of acceptable quality, although they lacked information in certain areas. The risk of publication bias was not significant. Based on the findings, methylated ctDNA in blood shows potential as a rule-in tool for lung cancer diagnosis but requires further research, possibly in combination with other biomarkers. Full article
(This article belongs to the Special Issue Liquid Biopsy in Lung Cancer)
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13 pages, 2111 KiB  
Article
Population-Based Clinical Cancer Registration in Germany
by Alexander Katalinic, Marco Halber, Martin Meyer, Maren Pflüger, Andrea Eberle, Alice Nennecke, Soo-Zin Kim-Wanner, Tobias Hartz, Kerstin Weitmann, Andreas Stang, Christina Justenhoven, Bernd Holleczek, Daniela Piontek, Ian Wittenberg, Annika Heßmer, Klaus Kraywinkel, Claudia Spix and Ron Pritzkuleit
Cancers 2023, 15(15), 3934; https://doi.org/10.3390/cancers15153934 - 2 Aug 2023
Cited by 21 | Viewed by 3297
Abstract
Introduction: In 2013, a new federal law obligated all German federal states to collect additional clinical data in population-based cancer registries as an active tool for monitoring and improving the quality of cancer care, increasing transparency and promoting health research. Now, 10 years [...] Read more.
Introduction: In 2013, a new federal law obligated all German federal states to collect additional clinical data in population-based cancer registries as an active tool for monitoring and improving the quality of cancer care, increasing transparency and promoting health research. Now, 10 years later, the current status of the expanded cancer registration is presented, including current figures on cancer in Germany. Methods: Reporting of cancer is mandatory for physicians, and about 5 to 10 reports from different healthcare providers are expected for each case. A uniform national dataset of about 130 items is used, and reports are usually sent electronically to the registry. We used the most recent data available from cancer registries up to the year of diagnosis in 2019. We calculated incidence rates and 5-year relative survival (5YRS) for common cancers. Data on clinical outcomes and benchmarking based on quality indicators (QIs) from guidelines were provided by the Cancer Registry Schleswig-Holstein (CR SH). Results: All federal state cancer registries met most of the previously defined national eligibility criteria. Approximately 505,000 cancer cases were registered in 2019, with breast, prostate, colorectal and lung cancer being the most common cancers. The age-standardised cancer incidence has slightly decreased during the last decade. and spatial heterogeneity can be observed within Germany. 5YRS for all cancers was 67% and 63% for women and men, respectively. Therapy data for rectal cancer in 2019–2021 from the CR SH are shown as an example: 69% of the registered patients underwent surgery, mostly with curative intent (84%) and tumour-free resection (91%). Radiotherapy was given to 33% of the patients, and chemotherapy was given to 40%. Three selected QIs showed differences between involved healthcare providers. Discussion: The implementation of population-based clinical cancer registration can be considered a success. Comprehensive recording of diagnosis, treatment and disease progression and the use of registry data for quality assurance, benchmarking and feedback have been implemented. Full article
(This article belongs to the Special Issue Advances in Cancer Data and Statistics)
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32 pages, 419 KiB  
Review
Antibody–Drug Conjugates: A Review of Approved Drugs and Their Clinical Level of Evidence
by Pooja Gogia, Hamza Ashraf, Sidharth Bhasin and Yiqing Xu
Cancers 2023, 15(15), 3886; https://doi.org/10.3390/cancers15153886 - 30 Jul 2023
Cited by 45 | Viewed by 10651
Abstract
Antibody–drug conjugates (ADCs) are an innovative family of agents assembled through linking cytotoxic drugs (payloads) covalently to monoclonal antibodies (mAbs) to be delivered to tumor tissue that express their particular antigen, with the theoretical advantage of an augmented therapeutic ratio. As of June [...] Read more.
Antibody–drug conjugates (ADCs) are an innovative family of agents assembled through linking cytotoxic drugs (payloads) covalently to monoclonal antibodies (mAbs) to be delivered to tumor tissue that express their particular antigen, with the theoretical advantage of an augmented therapeutic ratio. As of June 2023, eleven ADCs have been approved by the Food and Drug Administration (FDA) and are on the market. These drugs have been added to the therapeutic armamentarium of acute myeloblastic and lymphoblastic leukemias, various types of lymphoma, breast, gastric or gastroesophageal junction, lung, urothelial, cervical, and ovarian cancers. They have proven to deliver more potent and effective anti-tumor activities than standard practice in a wide variety of indications. In addition to targeting antigen-expressing tumor cells, bystander effects have been engineered to extend cytotoxic killing to low-antigen-expressing or negative tumor cells in the heterogenous tumor milieu. Inevitably, myelosuppression is a common side effect with most of the ADCs due to the effects of the cytotoxic payload. Also, other unique side effects are specific to the tissue antigen that is targeted for, such as the cardiac toxicity with Her-2 targeting ADCs, and the hemorrhagic side effects with the tissue factor (TF) targeting Tisotumab vedotin. Further exciting developments are centered in the strategies to improve the tolerability and efficacy of the ADCs to improve the therapeutic window; as well as the development of novel payloads including (1) peptide–drug conjugates (PDCs), with the peptide replacing the monoclonal antibody, rendering greater tumor penetration; (2) immune-stimulating antibody conjugates (ISACs), which upon conjugation of the antigen, cause an influx of pro-inflammatory cytokines to activate dendritic cells and harness an anti-tumor T-cell response; and (3) the use of radioactive isotopes as a payload to enhance cytotoxic activity. Full article
(This article belongs to the Section Cancer Therapy)
11 pages, 2608 KiB  
Article
Clinical Possibility of Caenorhabditis elegans as a Novel Evaluation Tool for Esophageal Cancer Patients Receiving Chemotherapy: A Prospective Study
by Yuta Sato, Manabu Futamura, Yoshihiro Tanaka, Hiroshi Tsuchiya, Masahiro Fukada, Toshiya Higashi, Itaru Yasufuku, Ryuichi Asai, Jesse Yu Tajima, Shigeru Kiyama, Hideyuki Hatakeyama, Masayo Morishita, Takaaki Hirotsu, Eric di Luccio, Takuma Ishihara, Nobuhisa Matsuhashi and Kazuhiro Yoshida
Cancers 2023, 15(15), 3870; https://doi.org/10.3390/cancers15153870 - 29 Jul 2023
Viewed by 3102
Abstract
Background: The nematode Caenorhabditis elegans (C. elegans) possesses a sophisticated sense of smell and is used for a novel cancer screening test that utilizes the chemotaxis index. We designed a single-institution, prospective study to confirm the ability of Nematode Nose (N-NOSE) [...] Read more.
Background: The nematode Caenorhabditis elegans (C. elegans) possesses a sophisticated sense of smell and is used for a novel cancer screening test that utilizes the chemotaxis index. We designed a single-institution, prospective study to confirm the ability of Nematode Nose (N-NOSE) to determine preoperative chemotherapy’s efficacy for esophageal cancer patients. Patients and Methods: We investigated the predictability of N-NOSE screening for the clinical effects of preoperative chemotherapy for esophageal cancer patients receiving radical surgery. The index reduction score (IRS) was calculated via the chemotaxis of C. elegans at three points: before treatment, before surgery, and after surgery, and its clinical relevance was examined. Result: Thirty-nine patients with esophageal cancer were enrolled from August 2020 to December 2021, and 30 patients receiving radical surgery were examined. Complete response or partial response was achieved in 23 cases (76.7%). When the target of the treatment effect was complete response only, the prediction accuracies of the IRS calculated by area under the curve was 0.85 (95% Confidence interval: 0.62–1) in clinically achieving complete response group, and the sensitivity and specificity were 1 and 0.63, respectively. Conclusion: Index reduction score using N-NOSE screening may reflect the efficacy of chemotherapy for esophageal cancer patients. A large-scale prospective study at multiple centers is desired in the future. Full article
(This article belongs to the Special Issue Oncology: State-of-the-Art Research and Initiatives in Japan)
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14 pages, 753 KiB  
Review
Neoadjuvant Immunotherapy for Patients with dMMR/MSI-High Gastrointestinal Cancers: A Changing Paradigm
by Muhammet Ozer, Charan Thej Reddy Vegivinti, Masood Syed, Morgan E. Ferrell, Cyndi Gonzalez Gomez, Svea Cheng, Jennifer Holder-Murray, Tullia Bruno, Anwaar Saeed and Ibrahim Halil Sahin
Cancers 2023, 15(15), 3833; https://doi.org/10.3390/cancers15153833 - 28 Jul 2023
Cited by 7 | Viewed by 4496
Abstract
Immune checkpoint inhibitors have revolutionized the management of mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) gastrointestinal cancers, particularly colorectal cancer. Cancers with the MMR-D/MSI-H genotype often carry a higher tumor mutation burden with frameshift alterations, leading to increased mutation-associated neoantigen (MANA) generation. The dramatic response [...] Read more.
Immune checkpoint inhibitors have revolutionized the management of mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) gastrointestinal cancers, particularly colorectal cancer. Cancers with the MMR-D/MSI-H genotype often carry a higher tumor mutation burden with frameshift alterations, leading to increased mutation-associated neoantigen (MANA) generation. The dramatic response seen with immune checkpoint inhibitors (ICIs), which are orchestrated by MANA-primed effector T cells, resulted in the rapid development of these novel therapeutics within the landscape of MSI-H gastrointestinal cancers. Recently, several clinical trials have utilized ICIs as potential neoadjuvant therapies for MSI-H gastrointestinal cancers and demonstrated deep clinical and pathological responses, creating opportunities for organ preservation. However, there are potential challenges to the neoadjuvant use of ICIs for certain disease types due to the clinical risk of overtreatment for a disease that can be cured through a surgery-only approach. In this review article, we discuss neoadjuvant management approaches with ICI therapy for patients with MSI-H gastrointestinal cancers, including those with oligometastatic disease. We also elaborate on potential challenges and opportunities for the neoadjuvant utilization of ICIs and provide further insight into the changing treatment paradigm of MMR-D/MSI-H gastrointestinal cancers. Full article
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11 pages, 7015 KiB  
Article
A Phase II Clinical Trial of Pembrolizumab Efficacy and Safety in Advanced Renal Medullary Carcinoma
by Chijioke Nze, Pavlos Msaouel, Mohamed H. Derbala, Bettzy Stephen, Abdulrahman Abonofal, Funda Meric-Bernstam, Nizar M. Tannir and Aung Naing
Cancers 2023, 15(15), 3806; https://doi.org/10.3390/cancers15153806 - 27 Jul 2023
Cited by 4 | Viewed by 2774
Abstract
Background. Renal medullary carcinoma (RMC) is one of most aggressive renal cell carcinomas and novel therapeutic strategies are therefore needed. Recent comprehensive molecular and immune profiling of RMC tissues revealed a highly inflamed phenotype, suggesting the potential therapeutic role for immune checkpoint therapies. [...] Read more.
Background. Renal medullary carcinoma (RMC) is one of most aggressive renal cell carcinomas and novel therapeutic strategies are therefore needed. Recent comprehensive molecular and immune profiling of RMC tissues revealed a highly inflamed phenotype, suggesting the potential therapeutic role for immune checkpoint therapies. We present the first prospective evaluation of an immune checkpoint inhibitor in a cohort of patients with RMC. Methods. A cohort of patients with locally advanced or metastatic RMC was treated with pembrolizumab 200 mg intravenously every 21 days in a phase II basket trial (ClinicalTrials.gov: NCT02721732). Responses were assessed by irRECIST. Tumor tissues were evaluated for PD-L1 expression and for tumor-infiltrating lymphocyte (TIL) levels. Somatic mutations were assessed by targeted next-generation sequencing. Results. A total of five patients were treated. All patients had advanced disease, with the majority of patients (60%) having metastatic disease at diagnosis. All patients had rapid disease progression despite pembrolizumab treatment, with a median time to progression of 8.7 weeks. One patient (patient 5) experienced sudden clinical progression immediately after treatment initiation and was thus taken off trial less than one week after receiving pembrolizumab. Conclusions. This prospective evaluation showed no evidence of clinical activity for pembrolizumab in patients with RMC, irrespective of PD-L1 or TIL levels. Full article
(This article belongs to the Special Issue Clinical and Translational Updates in Renal Cell Carcinoma)
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13 pages, 1190 KiB  
Article
Enhancing Triage Efficiency and Accuracy in Emergency Rooms for Patients with Metastatic Prostate Cancer: A Retrospective Analysis of Artificial Intelligence-Assisted Triage Using ChatGPT 4.0
by Georges Gebrael, Kamal Kant Sahu, Beverly Chigarira, Nishita Tripathi, Vinay Mathew Thomas, Nicolas Sayegh, Benjamin L. Maughan, Neeraj Agarwal, Umang Swami and Haoran Li
Cancers 2023, 15(14), 3717; https://doi.org/10.3390/cancers15143717 - 22 Jul 2023
Cited by 28 | Viewed by 4112
Abstract
Background: Accurate and efficient triage is crucial for prioritizing care and managing resources in emergency rooms. This study investigates the effectiveness of ChatGPT, an advanced artificial intelligence system, in assisting health providers with decision-making for patients presenting with metastatic prostate cancer, focusing on [...] Read more.
Background: Accurate and efficient triage is crucial for prioritizing care and managing resources in emergency rooms. This study investigates the effectiveness of ChatGPT, an advanced artificial intelligence system, in assisting health providers with decision-making for patients presenting with metastatic prostate cancer, focusing on the potential to improve both patient outcomes and resource allocation. Methods: Clinical data from patients with metastatic prostate cancer who presented to the emergency room between 1 May 2022 and 30 April 2023 were retrospectively collected. The primary outcome was the sensitivity and specificity of ChatGPT in determining whether a patient required admission or discharge. The secondary outcomes included the agreement between ChatGPT and emergency medicine physicians, the comprehensiveness of diagnoses, the accuracy of treatment plans proposed by both parties, and the length of medical decision making. Results: Of the 147 patients screened, 56 met the inclusion criteria. ChatGPT had a sensitivity of 95.7% in determining admission and a specificity of 18.2% in discharging patients. In 87.5% of cases, ChatGPT made the same primary diagnoses as physicians, with more accurate terminology use (42.9% vs. 21.4%, p = 0.02) and more comprehensive diagnostic lists (median number of diagnoses: 3 vs. 2, p < 0.001). Emergency Severity Index scores calculated by ChatGPT were not associated with admission (p = 0.12), hospital stay length (p = 0.91) or ICU admission (p = 0.54). Despite shorter mean word count (169 ± 66 vs. 272 ± 105, p < 0.001), ChatGPT was more likely to give additional treatment recommendations than physicians (94.3% vs. 73.5%, p < 0.001). Conclusions: Our hypothesis-generating data demonstrated that ChatGPT is associated with a high sensitivity in determining the admission of patients with metastatic prostate cancer in the emergency room. It also provides accurate and comprehensive diagnoses. These findings suggest that ChatGPT has the potential to assist health providers in improving patient triage in emergency settings, and may enhance both efficiency and quality of care provided by the physicians. Full article
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17 pages, 3021 KiB  
Review
Can Bee Venom Be Used as Anticancer Agent in Modern Medicine?
by Agata Małek, Maciej Strzemski, Joanna Kurzepa and Jacek Kurzepa
Cancers 2023, 15(14), 3714; https://doi.org/10.3390/cancers15143714 - 21 Jul 2023
Cited by 12 | Viewed by 4473
Abstract
Honey bee venom in its composition contains many biologically active peptides and enzymes that are effective in the fight against diseases of various etiologies. The history of the use of bee venom for medicinal purposes dates back thousands of years. There are many [...] Read more.
Honey bee venom in its composition contains many biologically active peptides and enzymes that are effective in the fight against diseases of various etiologies. The history of the use of bee venom for medicinal purposes dates back thousands of years. There are many reports in the literature on the pharmacological properties of bee venom and/or its main components, e.g., anti-arthritic, anti-inflammatory, anti-microbial or neuroprotective properties. In addition, both crude venom and melittin exhibit cytotoxic activity against a wide range of tumor cells, with significant anti-metastatic activity in pre-clinical studies. Due to the constantly increasing incidence of cancer, the development of new therapeutic strategies in oncology is a particular challenge for modern medicine. A review paper discusses the various properties of bee venom with an emphasis on its anticancer properties. For this purpose, the PubMed database was searched, and publications related to “bee”, “venom”, “cancer” from the last 10 years were selected. Full article
(This article belongs to the Topic Advances in Anti-Cancer Drugs)
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17 pages, 9854 KiB  
Article
The First Cold Atmospheric Plasma Phase I Clinical Trial for the Treatment of Advanced Solid Tumors: A Novel Treatment Arm for Cancer
by Jerome Canady, Saravana R. K. Murthy, Taisen Zhuang, Steven Gitelis, Aviram Nissan, Lawan Ly, Olivia Z. Jones, Xiaoqian Cheng, Mohammad Adileh, Alan T. Blank, Matthew W. Colman, Keith Millikan, Cristina O’Donoghue, Kerstin M. Stenson, Karen Ohara, Gal Schtrechman, Michael Keidar and Giacomo Basadonna
Cancers 2023, 15(14), 3688; https://doi.org/10.3390/cancers15143688 - 20 Jul 2023
Cited by 24 | Viewed by 4696
Abstract
Local regional recurrence (LRR) remains the primary cause of treatment failure in solid tumors despite advancements in cancer therapies. Canady Helios Cold Plasma (CHCP) is a novel Cold Atmospheric Plasma device that generates an Electromagnetic Field and Reactive Oxygen and Nitrogen Species to [...] Read more.
Local regional recurrence (LRR) remains the primary cause of treatment failure in solid tumors despite advancements in cancer therapies. Canady Helios Cold Plasma (CHCP) is a novel Cold Atmospheric Plasma device that generates an Electromagnetic Field and Reactive Oxygen and Nitrogen Species to induce cancer cell death. In the first FDA-approved Phase I trial (March 2020–April 2021), 20 patients with stage IV or recurrent solid tumors underwent surgical resection combined with intra-operative CHCP treatment. Safety was the primary endpoint; secondary endpoints were non-LRR, survival, cancer cell death, and the preservation of surrounding healthy tissue. CHCP did not impact intraoperative physiological data (p > 0.05) or cause any related adverse events. Overall response rates at 26 months for R0 and R0 with microscopic positive margin (R0-MPM) patients were 69% (95% CI, 19–40%) and 100% (95% CI, 100–100.0%), respectively. Survival rates for R0 (n = 7), R0-MPM (n = 5), R1 (n = 6), and R2 (n = 2) patients at 28 months were 86%, 40%, 67%, and 0%, respectively. The cumulative overall survival rate was 24% at 31 months (n = 20, 95% CI, 5.3–100.0). CHCP treatment combined with surgery is safe, selective towards cancer, and demonstrates exceptional LRR control in R0 and R0-MPM patients. (Clinical Trials identifier: NCT04267575). Full article
(This article belongs to the Section Clinical Research of Cancer)
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11 pages, 261 KiB  
Article
Effectiveness of Opioid Switching in Advanced Cancer Pain: A Prospective Observational Cohort Study
by Aaron K. Wong, Andrew A. Somogyi, Justin Rubio, Tien Dung Pham, Brian Le, Pal Klepstad and Jennifer Philip
Cancers 2023, 15(14), 3676; https://doi.org/10.3390/cancers15143676 - 19 Jul 2023
Cited by 3 | Viewed by 1678
Abstract
Opioid switching is a common practice of substituting one opioid for another to improve analgesia or adverse effects; however, it has limited evidence. This study aimed to examine the effectiveness of opioid switching in advanced cancer. This multi-center prospective cohort study recruited patients [...] Read more.
Opioid switching is a common practice of substituting one opioid for another to improve analgesia or adverse effects; however, it has limited evidence. This study aimed to examine the effectiveness of opioid switching in advanced cancer. This multi-center prospective cohort study recruited patients assessed to switch opioids (opioid switch group) or to continue ongoing opioid treatment (control group). Clinical data (demographics, opioids) and validated instruments (pain and adverse effects) were collected over two timepoints seven days apart. Descriptive analyses were utilized. Non-parametric tests were used to determine differences. Fifty-four participants were recruited (23 control group, 31 switch group). At the follow-up, opioid switching reduced pain (worst, average, and now) (p < 0.05), uncontrolled breakthrough pain (3-fold reduction, p = 0.008), and psychological distress (48% to 16%, p < 0.005). The switch group had a ≥25% reduction in the reported frequency of seven moderate-to-severe adverse effects (score ≥ 4), compared to a reduction in only one adverse effect in the control group. The control group experienced no significant pain differences at the follow-up. Opioid switching is effective at reducing pain, adverse effects, and psychological distress in a population with advanced cancer pain, to levels of satisfactory symptom control in most patients within 1 week. Full article
(This article belongs to the Special Issue Strategies for Cancer Pain Management)
18 pages, 7061 KiB  
Article
Validation of a Novel EUS-FNB-Derived Organoid Co-Culture System for Drug Screening in Patients with Pancreatic Cancer
by Simon Ezban Grützmeier, Bojan Kovacevic, Peter Vilmann, Charlotte Vestrup Rift, Linea Cecilie Melchior, Morten Orebo Holmström, Lene Brink, Hazem Hassan, John Gásdal Karstensen, Hanne Grossjohann, Deepthi Chiranth, Anders Toxværd, Carsten Palnæs Hansen, Estrid Høgdall, Jane Preuss Hasselby and Pia Klausen
Cancers 2023, 15(14), 3677; https://doi.org/10.3390/cancers15143677 - 19 Jul 2023
Cited by 4 | Viewed by 2723
Abstract
Cancer-associated fibroblasts (CAFs) have been shown to impact the chemosensitivity of patient-derived tumor organoids (PDTOs). However, the published literature comparing PDTO response to clinical outcome does not include CAFs in the models. Here, a co-culture model was created using PDTOs and CAFs derived [...] Read more.
Cancer-associated fibroblasts (CAFs) have been shown to impact the chemosensitivity of patient-derived tumor organoids (PDTOs). However, the published literature comparing PDTO response to clinical outcome does not include CAFs in the models. Here, a co-culture model was created using PDTOs and CAFs derived from endoscopic ultrasound-guided fine-needle biopsies (EUS-FNBs) for potential use in drug screening applications. Co-cultures were established, and growth was compared to monocultures using image metrics and a commercially available assay. We were able to establish and expand validated malignant PDTOs from 19.2% of adenocarcinomas from EUS-FNBs. CAFs could be established from 25% of the samples. The viability of PDTOs in the mixed cell co-culture could be isolated using image metrics. The addition of CAFs promoted PDTO growth in half of the established co-cultures. These results show that co-cultures can be established from tiny amounts of tissue provided by EUS-FNB. An increased growth of PDTOs was shown in co-cultures, suggesting that the present setup successfully models CAF–PDTO interaction. Furthermore, we demonstrated that standard validation techniques may be insufficient to detect contamination with normal cells in PDTO cultures established from primary tumor core biopsies. Full article
(This article belongs to the Special Issue Endoscopic Ultrasound in Gastrointestinal Cancers)
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15 pages, 1784 KiB  
Article
Incidence and Mortality of Malignant Brain Tumors after 20 Years of Mobile Use
by Mohy Uddin, Rozy Dhanta, Thejkiran Pitti, Diana Barsasella, Jeremiah Scholl, Wen-Shan Jian, Yu-Chuan (Jack) Li, Min-Huei Hsu and Shabbir Syed-Abdul
Cancers 2023, 15(13), 3492; https://doi.org/10.3390/cancers15133492 - 4 Jul 2023
Cited by 2 | Viewed by 4370
Abstract
(1) Objective: This population-based study was performed to examine the trends of incidence and deaths due to malignant neoplasm of the brain (MNB) in association with mobile phone usage for a period of 20 years (January 2000–December 2019) in Taiwan. (2) Methods: Pearson [...] Read more.
(1) Objective: This population-based study was performed to examine the trends of incidence and deaths due to malignant neoplasm of the brain (MNB) in association with mobile phone usage for a period of 20 years (January 2000–December 2019) in Taiwan. (2) Methods: Pearson correlation, regression analysis, and joinpoint regression analysis were used to examine the trends of incidence of MNB and deaths due to MNB in association with mobile phone usage. (3) Results: The findings indicate a trend of increase in the number of mobile phone users over the study period, accompanied by a slight rise in the incidence and death rates of MNB. The compound annual growth rates further support these observations, highlighting consistent growth in mobile phone users and a corresponding increase in MNB incidences and deaths. (4) Conclusions: The results suggest a weaker association between the growing number of mobile phone users and the rising rates of MNB, and no significant correlation was observed between MNB incidences and deaths and mobile phone usage. Ultimately, it is important to acknowledge that conclusive results cannot be drawn at this stage and further investigation is required by considering various other confounding factors and potential risks to obtain more definitive findings and a clearer picture. Full article
(This article belongs to the Special Issue Brain Tumor: Recent Advances and Challenges)
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17 pages, 4920 KiB  
Article
Vitamin D Receptor Antagonist MeTC7 Inhibits PD-L1
by Negar Khazan, Emily R. Quarato, Niloy A. Singh, Cameron W. A. Snyder, Taylor Moore, John P. Miller, Masato Yasui, Yuki Teramoto, Takuro Goto, Sabeeha Reshi, Jennifer Hong, Naixin Zhang, Diya Pandey, Priyanka Srivastava, Alexandra Morell, Hiroki Kawano, Yuko Kawano, Thomas Conley, Deepak M. Sahasrabudhe, Naohiro Yano, Hiroshi Miyamoto, Omar Aljitawi, Jane Liesveld, Michael W. Becker, Laura M. Calvi, Alexander S. Zhovmer, Erdem D. Tabdanov, Nikolay V. Dokholyan, David C. Linehan, Jeanne N. Hansen, Scott A. Gerber, Ashoke Sharon, Manoj K. Khera, Peter W. Jurutka, Natacha Rochel, Kyu Kwang Kim, Rachael B. Rowswell-Turner, Rakesh K. Singh and Richard G. Mooreadd Show full author list remove Hide full author list
Cancers 2023, 15(13), 3432; https://doi.org/10.3390/cancers15133432 - 30 Jun 2023
Cited by 4 | Viewed by 4596
Abstract
Small-molecule inhibitors of PD-L1 are postulated to control immune evasion in tumors similar to antibodies that target the PD-L1/PD-1 immune checkpoint axis. However, the identity of targetable PD-L1 inducers is required to develop small-molecule PD-L1 inhibitors. In this study, using chromatin immunoprecipitation (ChIP) [...] Read more.
Small-molecule inhibitors of PD-L1 are postulated to control immune evasion in tumors similar to antibodies that target the PD-L1/PD-1 immune checkpoint axis. However, the identity of targetable PD-L1 inducers is required to develop small-molecule PD-L1 inhibitors. In this study, using chromatin immunoprecipitation (ChIP) assay and siRNA, we demonstrate that vitamin D/VDR regulates PD-L1 expression in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cells. We have examined whether a VDR antagonist, MeTC7, can inhibit PD-L1. To ensure that MeTC7 inhibits VDR/PD-L1 without off-target effects, we examined competitive inhibition of VDR by MeTC7, utilizing ligand-dependent dimerization of VDR-RXR, RXR-RXR, and VDR-coactivators in a mammalian 2-hybrid (M2H) assay. MeTC7 inhibits VDR selectively, suppresses PD-L1 expression sparing PD-L2, and inhibits the cell viability, clonogenicity, and xenograft growth of AML cells. MeTC7 blocks AML/mesenchymal stem cells (MSCs) adhesion and increases the efferocytotic efficiency of THP-1 AML cells. Additionally, utilizing a syngeneic colorectal cancer model in which VDR/PD-L1 co-upregulation occurs in vivo under radiation therapy (RT), MeTC7 inhibits PD-L1 and enhances intra-tumoral CD8+T cells expressing lymphoid activation antigen-CD69. Taken together, MeTC7 is a promising small-molecule inhibitor of PD-L1 with clinical potential. Full article
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15 pages, 1562 KiB  
Article
Assessing the Performance of a Novel Stool-Based Microbiome Test That Predicts Response to First Line Immune Checkpoint Inhibitors in Multiple Cancer Types
by Irina Robinson, Maximilian Johannes Hochmair, Manuela Schmidinger, Gudrun Absenger, Martin Pichler, Van Anh Nguyen, Erika Richtig, Barbara Margaretha Rainer, Leyla Ay, Christian Jansen, Cátia Pacífico, Alexander Knabl, Barbara Sladek, Nikolaus Gasche and Arschang Valipour
Cancers 2023, 15(13), 3268; https://doi.org/10.3390/cancers15133268 - 21 Jun 2023
Cited by 2 | Viewed by 3156
Abstract
The intestinal microbiome is by now an undebatable key player in the clinical outcome of ICI therapies. However, no microbiome profiling method to aid therapy decision is yet validated. We conducted a multi-centric study in patients with stage III/IV melanoma, NSCLC, or RCC [...] Read more.
The intestinal microbiome is by now an undebatable key player in the clinical outcome of ICI therapies. However, no microbiome profiling method to aid therapy decision is yet validated. We conducted a multi-centric study in patients with stage III/IV melanoma, NSCLC, or RCC receiving ICI treatment. The stool microbiome profile of 63 patients was analyzed with BiomeOne®, a microbiome-based algorithm that anticipates whether a patient will achieve clinical benefit with ICIs prior to therapy initiation. Classification of patient samples as Rs and NRs was achieved with a sensitivity of 81% and a specificity of 50% in this validation cohort. An ICI-favorable response was characterized by an intestinal microbiome rich in bacteria such as Oscillospira sp., Clostridia UCG-014, Lachnospiraceae UCG-010 sp., Prevotella copri, and a decrease in Sutterella sp., Lactobacillales, and Streptococcus sp. Patients who developed immune-related adverse events (irAEs) had an overall increased microbial diversity and richness, and a stool microbiome depleted in Agathobacter. When compared with the programmed death-ligand 1 (PD-L1) expression test in the subcohort of NSCLC patients (n = 38), BiomeOne® exhibited a numerically higher sensitivity (78.6%) in identifying responders when compared with the PD-L1 test (67.9%). This study provides an evaluation of BiomeOne®, the first microbiome-based test for prediction of ICI response, to achieve market authorization. Validation with further indications and expansion to other microbiome-based interventions will be essential to bring microbiome-based diagnostics into standard clinical practice. Full article
(This article belongs to the Special Issue Artificial Intelligence and Machine Learning in Precision Oncology)
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15 pages, 1033 KiB  
Review
New Approaches to Targeted Therapy in Melanoma
by Manuel Felipe Fernandez, Jacob Choi and Jeffrey Sosman
Cancers 2023, 15(12), 3224; https://doi.org/10.3390/cancers15123224 - 17 Jun 2023
Cited by 12 | Viewed by 3459
Abstract
It was just slightly more than a decade ago when metastatic melanoma carried a dismal prognosis with few, if any, effective therapies. Since then, the evolution of cancer immunotherapy has led to new and effective treatment approaches for melanoma. However, despite these advances, [...] Read more.
It was just slightly more than a decade ago when metastatic melanoma carried a dismal prognosis with few, if any, effective therapies. Since then, the evolution of cancer immunotherapy has led to new and effective treatment approaches for melanoma. However, despite these advances, a sizable portion of patients with advanced melanoma have de novo or acquired resistance to immune checkpoint inhibitors. At the same time, therapies (BRAF plus MEK inhibitors) targeting the BRAFV600 mutations found in 40–50% of cutaneous melanomas have also been critical for optimizing management and improving patient outcomes. Even though immunotherapy has been established as the initial therapy in most patients with cutaneous melanoma, subsequent effective therapy is limited to BRAFV600 melanoma. For all other melanoma patients, driver mutations have not been effectively targeted. Numerous efforts are underway to target melanomas with NRAS mutations, NF-1 LOF mutations, and other genetic alterations leading to activation of the MAP kinase pathway. In this era of personalized medicine, we will review the current genetic landscape, molecular classifications, emerging drug targets, and the potential for combination therapies for non-BRAFV600 melanoma. Full article
(This article belongs to the Collection Emerging Therapeutics in Advanced Melanoma)
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15 pages, 7002 KiB  
Article
Spatial Transcriptomics Identifies Expression Signatures Specific to Lacrimal Gland Adenoid Cystic Carcinoma Cells
by Acadia H. M. Moeyersoms, Ryan A. Gallo, Michelle G. Zhang, Vasileios Stathias, Michelle M. Maeng, Dawn Owens, Rayan Abou Khzam, Yoseph Sayegh, Cynthia Maza, Sander R. Dubovy, David T. Tse and Daniel Pelaez
Cancers 2023, 15(12), 3211; https://doi.org/10.3390/cancers15123211 - 16 Jun 2023
Cited by 4 | Viewed by 2864
Abstract
Although primary tumors of the lacrimal gland are rare, adenoid cystic carcinoma (ACC) is the most common and lethal epithelial lacrimal gland malignancy. Traditional management of lacrimal gland adenoid cystic carcinoma (LGACC) involves the removal of the eye and surrounding socket contents, followed [...] Read more.
Although primary tumors of the lacrimal gland are rare, adenoid cystic carcinoma (ACC) is the most common and lethal epithelial lacrimal gland malignancy. Traditional management of lacrimal gland adenoid cystic carcinoma (LGACC) involves the removal of the eye and surrounding socket contents, followed by chemoradiation. Even with this radical treatment, the 10-year survival rate for LGACC is 20% given the propensity for recurrence and metastasis. Due to the rarity of LGACC, its pathobiology is not well-understood, leading to difficulties in diagnosis, treatment, and effective management. Here, we integrate bulk RNA sequencing (RNA-seq) and spatial transcriptomics to identify a specific LGACC gene signature that can inform novel targeted therapies. Of the 3499 differentially expressed genes identified by bulk RNA-seq, the results of our spatial transcriptomic analysis reveal 15 upregulated and 12 downregulated genes that specifically arise from LGACC cells, whereas fibroblasts, reactive fibrotic tissue, and nervous and skeletal muscle account for the remaining bulk RNA-seq signature. In light of the analysis, we identified a transitional state cell or stem cell cluster. The results of the pathway analysis identified the upregulation of PI3K-Akt signaling, IL-17 signaling, and multiple other cancer pathways. This study provides insights into the molecular and cellular landscape of LGACC, which can inform new, targeted therapies to improve patient outcomes. Full article
(This article belongs to the Section Molecular Cancer Biology)
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24 pages, 3755 KiB  
Review
Tumor Microenvironment as a Therapeutic Target in Melanoma Treatment
by Naji Kharouf, Thomas W. Flanagan, Sofie-Yasmin Hassan, Hosam Shalaby, Marla Khabaz, Sarah-Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis and Mohamed Hassan
Cancers 2023, 15(12), 3147; https://doi.org/10.3390/cancers15123147 - 11 Jun 2023
Cited by 8 | Viewed by 3726
Abstract
The role of the tumor microenvironment in tumor growth and therapy has recently attracted more attention in research and drug development. The ability of the microenvironment to trigger tumor maintenance, progression, and resistance is the main cause for treatment failure and tumor relapse. [...] Read more.
The role of the tumor microenvironment in tumor growth and therapy has recently attracted more attention in research and drug development. The ability of the microenvironment to trigger tumor maintenance, progression, and resistance is the main cause for treatment failure and tumor relapse. Accumulated evidence indicates that the maintenance and progression of tumor cells is determined by components of the microenvironment, which include stromal cells (endothelial cells, fibroblasts, mesenchymal stem cells, and immune cells), extracellular matrix (ECM), and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles). As a solid tumor, melanoma is not only a tumor mass of monolithic tumor cells, but it also contains supporting stroma, ECM, and soluble molecules. Melanoma cells are continuously in interaction with the components of the microenvironment. In the present review, we focus on the role of the tumor microenvironment components in the modulation of tumor progression and treatment resistance as well as the impact of the tumor microenvironment as a therapeutic target in melanoma. Full article
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21 pages, 4028 KiB  
Review
Innovation in Radionuclide Therapy for the Treatment of Prostate Cancers: Radiochemical Perspective and Recent Therapeutic Practices
by Emmanuel Deshayes, Cyril Fersing, Constance Thibault, Mathieu Roumiguie, Philippe Pourquier and Nadine Houédé
Cancers 2023, 15(12), 3133; https://doi.org/10.3390/cancers15123133 - 10 Jun 2023
Cited by 4 | Viewed by 3247
Abstract
Prostate cancer represents the second cause of death by cancer in males in western countries. While early-stage diseases are accessible to surgery and/or external radiotherapy, advanced metastatic prostate cancers are primarily treated with androgen deprivation therapy, to which new generation androgen receptor antagonists [...] Read more.
Prostate cancer represents the second cause of death by cancer in males in western countries. While early-stage diseases are accessible to surgery and/or external radiotherapy, advanced metastatic prostate cancers are primarily treated with androgen deprivation therapy, to which new generation androgen receptor antagonists or taxane-based chemotherapies are added in the case of tumor relapse. Nevertheless, patients become invariably resistant to castration with a median survival that rarely exceeds 3 years. This fostered the search for alternative strategies, independent of the androgen receptor signaling pathway. In this line, radionuclide therapies may represent an interesting option as they could target either the microenvironment of sclerotic bone metastases with the use of radiopharmaceuticals containing samarium-153, strontium-89 or radium-223 or tumor cells expressing the prostate-specific membrane antigen (PSMA), a protein found at the surface of prostate cancer cells. This review gives highlights the chemical properties of radioligands targeting prostate cancer cells and recapitulates the clinical trials evaluating the efficacy of radionuclide therapies, alone or in combination with other approved treatments, in patients with castration-resistant prostate tumors. It discusses some of the encouraging results obtained, especially the benefit on overall survival that was reported with [177Lu]-PSMA-617. It also addresses the specific requirements for the use of this particular class of drugs, both in terms of medical staff coordination and adapted infrastructures for efficient radioprotection. Full article
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16 pages, 4543 KiB  
Article
Immuno-PET Imaging of Tumour PD-L1 Expression in Glioblastoma
by Gitanjali Sharma, Marta C. Braga, Chiara Da Pieve, Wojciech Szopa, Tatjana Starzetz, Karl H. Plate, Wojciech Kaspera and Gabriela Kramer-Marek
Cancers 2023, 15(12), 3131; https://doi.org/10.3390/cancers15123131 - 9 Jun 2023
Cited by 5 | Viewed by 3783
Abstract
There is no established method to assess the PD-L1 expression in brain tumours. Therefore, we investigated the suitability of affibody molecule (ZPD-L1) radiolabelled with F-18 (Al18F) and Ga-68 to measure the expression of PD-L1 in xenograft mouse models of [...] Read more.
There is no established method to assess the PD-L1 expression in brain tumours. Therefore, we investigated the suitability of affibody molecule (ZPD-L1) radiolabelled with F-18 (Al18F) and Ga-68 to measure the expression of PD-L1 in xenograft mouse models of GBM. Mice bearing subcutaneous and orthotopic tumours were imaged 1 h post-radioconjugate administration. Ex vivo biodistribution studies and immunohistochemistry (IHC) staining were performed. Tumoural PD-L1 expression and CD4+/CD8+ tumour-infiltrating lymphocytes were evaluated in human GBM specimens. ZPD-L1 was radiolabelled with radiochemical yields of 32.2 ± 4.4% (F-18) and 73.3 ± 1.8% (Ga-68). The cell-associated radioactivity in vitro was consistent with PD-L1 expression levels assessed with flow cytometry. In vivo imaging demonstrated that 18F-AlF-NOTA-ZPD-L1 can distinguish between PD-L1 high-expressing tumours (U87-MGvIII) and PD-L1-negative ones (H292PD-L1Ko). The radioconjugate was quickly cleared from the blood and normal tissues, allowing for high-contrast images of brain tumours as early as 1 h post-injection. 68Ga-NOTA-ZPD-L1 showed heterogeneous and diffuse accumulation that corresponded to the extensively infiltrating GCGR-E55 tumours involving contiguous lobes of the brain. Lastly, 39% of analysed GBM patient samples showed PD-L1+ staining of tumour cells that was associated with elevated levels of CD4+ and CD8+ lymphocytes. Our results suggest that the investigated radioconjugates are very promising agents with the potential to facilitate the future design of treatment regimens for GBM patients. Full article
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19 pages, 1853 KiB  
Review
Endoscopic Resection of Early Gastric Cancer and Pre-Malignant Gastric Lesions
by Ana Clara Vasconcelos, Mário Dinis-Ribeiro and Diogo Libânio
Cancers 2023, 15(12), 3084; https://doi.org/10.3390/cancers15123084 - 7 Jun 2023
Cited by 7 | Viewed by 5656
Abstract
Early gastric cancer comprises gastric malignancies that are confined to the mucosa or submucosa, irrespective of lymph node metastasis. Endoscopic resection is currently pivotal for the management of such early lesions, and it is the recommended treatment for tumors presenting a very low [...] Read more.
Early gastric cancer comprises gastric malignancies that are confined to the mucosa or submucosa, irrespective of lymph node metastasis. Endoscopic resection is currently pivotal for the management of such early lesions, and it is the recommended treatment for tumors presenting a very low risk of lymph node metastasis. In general, these lesions consist of two groups of differentiated mucosal adenocarcinomas: non-ulcerated lesions (regardless of their size) and small ulcerated lesions. Endoscopic submucosal dissection is the technique of choice in most cases. This procedure has high rates of complete histological resection while maintaining gastric anatomy and its functions, resulting in fewer adverse events than surgery and having a lesser impact on patient-reported quality of life. Nonetheless, approximately 20% of resected lesions do not fulfill curative criteria and demand further treatment, highlighting the importance of patient selection. Additionally, the preservation of the stomach results in a moderate risk of metachronous lesions, which underlines the need for surveillance. We review the current evidence regarding the endoscopic treatment of early gastric cancer, including the short-and long-term results and management after resection. Full article
(This article belongs to the Special Issue The Application of Endoscopy in Gastrointestinal Cancers)
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13 pages, 3868 KiB  
Article
Comparing Oncologic Outcomes and Toxicity for Combined Modality Therapy vs. Carbon-Ion Radiotherapy for Previously Irradiated Locally Recurrent Rectal Cancer
by Elizabeth B. Jeans, Daniel K. Ebner, Hirotoshi Takiyama, Kaitlin Qualls, Danielle A. Cunningham, Mark R. Waddle, Krishan R. Jethwa, William S. Harmsen, Joleen M. Hubbard, Eric J. Dozois, Kellie L. Mathis, Hiroshi Tsuji, Kenneth W. Merrell, Christopher L. Hallemeier, Anita Mahajan, Shigeru Yamada, Robert L. Foote and Michael G. Haddock
Cancers 2023, 15(11), 3057; https://doi.org/10.3390/cancers15113057 - 5 Jun 2023
Cited by 5 | Viewed by 1663
Abstract
No standard treatment paradigm exists for previously irradiated locally recurrent rectal cancer (PILRRC). Carbon-ion radiotherapy (CIRT) may improve oncologic outcomes and reduce toxicity compared with combined modality therapy (CMT). Eighty-five patients treated at Institution A with CIRT alone (70.4 Gy/16 fx) and eighty-six [...] Read more.
No standard treatment paradigm exists for previously irradiated locally recurrent rectal cancer (PILRRC). Carbon-ion radiotherapy (CIRT) may improve oncologic outcomes and reduce toxicity compared with combined modality therapy (CMT). Eighty-five patients treated at Institution A with CIRT alone (70.4 Gy/16 fx) and eighty-six at Institution B with CMT (30 Gy/15 fx chemoradiation, resection, intraoperative electron radiotherapy (IOERT)) between 2006 and 2019 were retrospectively compared. Overall survival (OS), pelvic re-recurrence (PR), distant metastasis (DM), or any disease progression (DP) were analyzed with the Kaplan–Meier model, with outcomes compared using the Cox proportional hazards model. Acute and late toxicities were compared, as was the 2-year cost. The median time to follow-up or death was 6.5 years. Median OS in the CIRT and CMT cohorts were 4.5 and 2.6 years, respectively (p ≤ 0.01). No difference was seen in the cumulative incidence of PR (p = 0.17), DM (p = 0.39), or DP (p = 0.19). Lower acute grade ≥ 2 skin and GI/GU toxicity and lower late grade ≥ 2 GU toxicities were associated with CIRT. Higher 2-year cumulative costs were associated with CMT. Oncologic outcomes were similar for patients treated with CIRT or CMT, although patient morbidity and cost were lower with CIRT, and CIRT was associated with longer OS. Prospective comparative studies are needed. Full article
(This article belongs to the Section Cancer Therapy)
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17 pages, 5649 KiB  
Article
deepPERFECT: Novel Deep Learning CT Synthesis Method for Expeditious Pancreatic Cancer Radiotherapy
by Hamed Hooshangnejad, Quan Chen, Xue Feng, Rui Zhang and Kai Ding
Cancers 2023, 15(11), 3061; https://doi.org/10.3390/cancers15113061 - 5 Jun 2023
Cited by 9 | Viewed by 2159
Abstract
Major sources of delay in the standard of care RT workflow are the need for multiple appointments and separate image acquisition. In this work, we addressed the question of how we can expedite the workflow by synthesizing planning CT from diagnostic CT. This [...] Read more.
Major sources of delay in the standard of care RT workflow are the need for multiple appointments and separate image acquisition. In this work, we addressed the question of how we can expedite the workflow by synthesizing planning CT from diagnostic CT. This idea is based on the theory that diagnostic CT can be used for RT planning, but in practice, due to the differences in patient setup and acquisition techniques, separate planning CT is required. We developed a generative deep learning model, deepPERFECT, that is trained to capture these differences and generate deformation vector fields to transform diagnostic CT into preliminary planning CT. We performed detailed analysis both from an image quality and a dosimetric point of view, and showed that deepPERFECT enabled the preliminary RT planning to be used for preliminary and early plan dosimetric assessment and evaluation. Full article
(This article belongs to the Special Issue Radiation Therapy for Pancreatic Cancer)
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17 pages, 1467 KiB  
Article
Analysis of the Gut Microbiome and Dietary Habits in Metastatic Melanoma Patients with a Complete and Sustained Response to Immunotherapy
by Marin Golčić, Luka Simetić, Davorin Herceg, Krešimir Blažičević, Gordana Kenđel Jovanović, Ivan Dražić, Andrej Belančić, Nataša Skočibušić, Dora Palčevski, Igor Rubinić, Vera Vlahović-Palčevski, Tea Majnarić, Renata Dobrila-Dintinjana and Stjepko Pleština
Cancers 2023, 15(11), 3052; https://doi.org/10.3390/cancers15113052 - 4 Jun 2023
Cited by 4 | Viewed by 2496
Abstract
Immunotherapy has improved the prognosis of metastatic melanoma patients, although most patients do not achieve a complete response. While specific gut microbiome and dietary habits might influence treatment success, there is a lack of concordance between the studies, potentially due to dichotomizing patients [...] Read more.
Immunotherapy has improved the prognosis of metastatic melanoma patients, although most patients do not achieve a complete response. While specific gut microbiome and dietary habits might influence treatment success, there is a lack of concordance between the studies, potentially due to dichotomizing patients only into responders and non-responders. The aim of this study was to elucidate whether metastatic melanoma patients with complete and sustained response to immunotherapy exhibit differences in gut microbiome composition among themselves, and whether those differences were associated with specific dietary habits. Shotgun metagenomic sequencing revealed that patients who exhibited a complete response after more than 9 months of treatment (late responders) exhibited a significantly higher beta-diversity (p = 0.02), with a higher abundance of Coprococcus comes (LDA 3.548, p = 0.010), Bifidobacterium pseudocatenulatum (LDA 3.392, p = 0.024), and lower abundance of Prevotellaceae (p = 0.04) compared to early responders. Furthermore, late responders exhibited a different diet profile, with a significantly lower intake of proteins and sweets and a higher intake of flavones (p < 0.05). The research showed that metastatic melanoma patients with a complete and sustained response to immunotherapy were a heterogeneous group. Patients with a late complete response exhibited microbiome and dietary habits which were previously associated with an improved response to immunotherapy. Full article
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18 pages, 4551 KiB  
Article
Follicular Helper and Regulatory T Cells Drive the Development of Spontaneous Epstein–Barr Virus Lymphoproliferative Disorder
by Elshafa Hassan Ahmed, Mark Lustberg, Claire Hale, Shelby Sloan, Charlene Mao, Xiaoli Zhang, Hatice Gulcin Ozer, Sarah Schlotter, Porsha L. Smith, Frankie Jeney, Wing Keung Chan, Bonnie K. Harrington, Christoph Weigel, Eric Brooks, Haley L. Klimaszewski, Christopher C. Oakes, Tamrat Abebe, Muntaser E. Ibrahim, Lapo Alinari, Gregory K. Behbehani, Polina Shindiapina, Michael A. Caligiuri and Robert A. Baiocchiadd Show full author list remove Hide full author list
Cancers 2023, 15(11), 3046; https://doi.org/10.3390/cancers15113046 - 3 Jun 2023
Cited by 2 | Viewed by 3106
Abstract
Epstein–Barr virus (EBV) is a ubiquitous herpes virus associated with various cancers. EBV establishes latency with life-long persistence in memory B-cells and can reactivate lytic infection placing immunocompromised individuals at risk for EBV-driven lymphoproliferative disorders (EBV-LPD). Despite the ubiquity of EBV, only a [...] Read more.
Epstein–Barr virus (EBV) is a ubiquitous herpes virus associated with various cancers. EBV establishes latency with life-long persistence in memory B-cells and can reactivate lytic infection placing immunocompromised individuals at risk for EBV-driven lymphoproliferative disorders (EBV-LPD). Despite the ubiquity of EBV, only a small percentage of immunocompromised patients (~20%) develop EBV-LPD. Engraftment of immunodeficient mice with peripheral blood mononuclear cells (PBMCs) from healthy EBV-seropositive donors leads to spontaneous, malignant, human B-cell EBV-LPD. Only about 20% of EBV+ donors induce EBV-LPD in 100% of engrafted mice (High-Incidence, HI), while another 20% of donors never generate EBV-LPD (No-Incidence, NI). Here, we report HI donors to have significantly higher basal T follicular helper (Tfh) and regulatory T-cells (Treg), and depletion of these subsets prevents/delays EBV-LPD. Transcriptomic analysis of CD4+ T cells from ex vivo HI donor PBMC revealed amplified cytokine and inflammatory gene signatures. HI vs. NI donors showed a marked reduction in IFNγ production to EBV latent and lytic antigen stimulation. In addition, we observed abundant myeloid-derived suppressor cells in HI donor PBMC that decreased CTL proliferation in co-cultures with autologous EBV+ lymphoblasts. Our findings identify potential biomarkers that may identify individuals at risk for EBV-LPD and suggest possible strategies for prevention. Full article
(This article belongs to the Special Issue Epstein-Barr Virus-Associated Cancers: From Pathogenesis to Treatment)
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16 pages, 1062 KiB  
Article
Cytogenetic Assessment and Risk Stratification in Myelofibrosis with Optical Genome Mapping
by Álvaro Díaz-González, Elvira Mora, Gayane Avetisyan, Santiago Furió, Rosalía De la Puerta, José Vicente Gil, Alessandro Liquori, Eva Villamón, Carmen García-Hernández, Marta Santiago, Cristian García-Ruiz, Marta Llop, Blanca Ferrer-Lores, Eva Barragán, Silvia García-Palomares, Empar Mayordomo, Irene Luna, Ana Vicente, Lourdes Cordón, Leonor Senent, Alberto Álvarez-Larrán, José Cervera, Javier De la Rubia, Juan Carlos Hernández-Boluda and Esperanza Suchadd Show full author list remove Hide full author list
Cancers 2023, 15(11), 3039; https://doi.org/10.3390/cancers15113039 - 2 Jun 2023
Viewed by 2582
Abstract
Cytogenetic assessment in myelofibrosis is essential for risk stratification and patient management. However, an informative karyotype is unavailable in a significant proportion of patients. Optical genome mapping (OGM) is a promising technique that allows for a high-resolution assessment of chromosomal aberrations (structural variants, [...] Read more.
Cytogenetic assessment in myelofibrosis is essential for risk stratification and patient management. However, an informative karyotype is unavailable in a significant proportion of patients. Optical genome mapping (OGM) is a promising technique that allows for a high-resolution assessment of chromosomal aberrations (structural variants, copy number variants, and loss of heterozygosity) in a single workflow. In this study, peripheral blood samples from a series of 21 myelofibrosis patients were analyzed via OGM. We assessed the clinical impact of the application of OGM for disease risk stratification using the DIPSS-plus, GIPSS, and MIPSS70+v2 prognostic scores compared with the standard-of-care approach. OGM, in combination with NGS, allowed for risk classification in all cases, compared to only 52% when conventional techniques were used. Cases with unsuccessful karyotypes (n = 10) using conventional techniques were fully characterized using OGM. In total, 19 additional cryptic aberrations were identified in 9 out of 21 patients (43%). No alterations were found via OGM in 4/21 patients with previously normal karyotypes. OGM upgraded the risk category for three patients with available karyotypes. This is the first study using OGM in myelofibrosis. Our data support that OGM is a valuable tool that can greatly contribute to improve disease risk stratification in myelofibrosis patients. Full article
(This article belongs to the Special Issue Diagnosis of Hematologic Malignancies)
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19 pages, 3798 KiB  
Article
An Aminosteroid Derivative Shows Higher In Vitro and In Vivo Potencies than Gold Standard Drugs in Androgen-Dependent Prostate Cancer Models
by Donald Poirier, Jenny Roy, René Maltais, Cindy Weidmann and Étienne Audet-Walsh
Cancers 2023, 15(11), 3033; https://doi.org/10.3390/cancers15113033 - 2 Jun 2023
Viewed by 5105
Abstract
The aminosteroid derivative RM-581 blocks with high potency the growth of androgen-dependent (AR+) prostate cancer VCaP, 22Rv1, and LAPC-4 cells. Notably, RM-581 demonstrated superior antiproliferative activity in LAPC-4 cells compared to enzalutamide and abiraterone, two drugs that exhibited a synergistic effect [...] Read more.
The aminosteroid derivative RM-581 blocks with high potency the growth of androgen-dependent (AR+) prostate cancer VCaP, 22Rv1, and LAPC-4 cells. Notably, RM-581 demonstrated superior antiproliferative activity in LAPC-4 cells compared to enzalutamide and abiraterone, two drugs that exhibited a synergistic effect in combination with RM-581. These findings suggest that RM-581 may have an action that is not directly associated with the hormonal pathway of androgens. Furthermore, RM-581 completely blocks tumor growth in LAPC-4 xenografts when given orally at 3, 10, and 30 mg/kg in non-castrated (intact) nude mice. During this study, an accumulation of RM-581 was observed in tumors compared to plasma (3.3–10 folds). Additionally, the level of fatty acids (FA) increased in the tumors and livers of mice treated with RM-581 but not in plasma. The increase was greater in unsaturated FA (21–28%) than in saturated FA (7–11%). The most affected FA were saturated palmitic acid (+16%), monounsaturated oleic acid (+34%), and di-unsaturated linoleic acid (+56%), i.e., the 3 most abundant FA, with a total of 55% of the 56 FA measured. For cholesterol levels, there was no significant difference in the tumor, liver, or plasma of mice treated or not with RM-581. Another important result was the innocuity of RM-581 in mice during a 28-day xenograft experiment and a 7-week dose-escalation study, suggesting a favorable safety window for this new promising drug candidate when given orally. Full article
(This article belongs to the Special Issue Novel Drugs for Prostate Cancer)
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13 pages, 1789 KiB  
Article
Plasma Metabolomics Predicts Chemotherapy Response in Advanced Pancreatic Cancer
by Hayato Muranaka, Andrew Hendifar, Arsen Osipov, Natalie Moshayedi, Veronica Placencio-Hickok, Nicholas Tatonetti, Aleksandr Stotland, Sarah Parker, Jennifer Van Eyk, Stephen J. Pandol, Neil A. Bhowmick and Jun Gong
Cancers 2023, 15(11), 3020; https://doi.org/10.3390/cancers15113020 - 1 Jun 2023
Cited by 5 | Viewed by 2140
Abstract
Pancreatic cancer (PC) is one of the deadliest cancers. Developing biomarkers for chemotherapeutic response prediction is crucial for improving the dismal prognosis of advanced-PC patients (pts). To evaluate the potential of plasma metabolites as predictors of the response to chemotherapy for PC patients, [...] Read more.
Pancreatic cancer (PC) is one of the deadliest cancers. Developing biomarkers for chemotherapeutic response prediction is crucial for improving the dismal prognosis of advanced-PC patients (pts). To evaluate the potential of plasma metabolites as predictors of the response to chemotherapy for PC patients, we analyzed plasma metabolites using high-performance liquid chromatography–mass spectrometry from 31 cachectic, advanced-PC subjects enrolled into the PANCAX-1 (NCT02400398) prospective trial to receive a jejunal tube peptide-based diet for 12 weeks and who were planned for palliative chemotherapy. Overall, there were statistically significant differences in the levels of intermediates of multiple metabolic pathways in pts with a partial response (PR)/stable disease (SD) vs. progressive disease (PD) to chemotherapy. When stratified by the chemotherapy regimen, PD after 5-fluorouracil-based chemotherapy (e.g., FOLFIRINOX) was associated with decreased levels of amino acids (AAs). For gemcitabine-based chemotherapy (e.g., gemcitabine/nab-paclitaxel), PD was associated with increased levels of intermediates of glycolysis, the TCA cycle, nucleoside synthesis, and bile acid metabolism. These results demonstrate the feasibility of plasma metabolomics in a prospective cohort of advanced-PC patients for assessing the effect of enteral feeding as their primary source of nutrition. Metabolic signatures unique to FOLFIRINOX or gemcitabine/nab-paclitaxel may be predictive of a patient’s response and warrant further study. Full article
(This article belongs to the Special Issue Lipids and Small Metabolites in Cancer)
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19 pages, 1166 KiB  
Systematic Review
Drug Repurposing in Oncology: A Systematic Review of Randomized Controlled Clinical Trials
by Ignatios Ioakeim-Skoufa, Natalia Tobajas-Ramos, Enrica Menditto, Mercedes Aza-Pascual-Salcedo, Antonio Gimeno-Miguel, Valentina Orlando, Francisca González-Rubio, Ana Fanlo-Villacampa, Carmen Lasala-Aza, Ewelina Ostasz and Jorge Vicente-Romero
Cancers 2023, 15(11), 2972; https://doi.org/10.3390/cancers15112972 - 30 May 2023
Cited by 7 | Viewed by 4024
Abstract
Quality pharmacological treatment can improve survival in many types of cancer. Drug repurposing offers advantages in comparison with traditional drug development procedures, reducing time and risk. This systematic review identified the most recent randomized controlled clinical trials that focus on drug repurposing in [...] Read more.
Quality pharmacological treatment can improve survival in many types of cancer. Drug repurposing offers advantages in comparison with traditional drug development procedures, reducing time and risk. This systematic review identified the most recent randomized controlled clinical trials that focus on drug repurposing in oncology. We found that only a few clinical trials were placebo-controlled or standard-of-care-alone-controlled. Metformin has been studied for potential use in various types of cancer, including prostate, lung, and pancreatic cancer. Other studies assessed the possible use of the antiparasitic agent mebendazole in colorectal cancer and of propranolol in multiple myeloma or, when combined with etodolac, in breast cancer. We were able to identify trials that study the potential use of known antineoplastics in other non-oncological conditions, such as imatinib for severe coronavirus disease in 2019 or a study protocol aiming to assess the possible repurposing of leuprolide for Alzheimer’s disease. Major limitations of these clinical trials were the small sample size, the high clinical heterogeneity of the participants regarding the stage of the neoplastic disease, and the lack of accounting for multimorbidity and other baseline clinical characteristics. Drug repurposing possibilities in oncology must be carefully examined with well-designed trials, considering factors that could influence prognosis. Full article
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14 pages, 1409 KiB  
Article
Efficacy of Tango Argentino for Cancer-Associated Fatigue and Quality of Life in Breast Cancer Survivors: A Randomized Controlled Trial
by Friedemann Schad, Thomas Rieser, Sarah Becker, Jessica Groß, Harald Matthes, Shiao Li Oei and Anja Thronicke
Cancers 2023, 15(11), 2920; https://doi.org/10.3390/cancers15112920 - 26 May 2023
Cited by 3 | Viewed by 3631
Abstract
Background: Persistent impairments of quality of life—in particular, cancer-associated fatigue—are a major limitation for breast cancer survivors. As physical activity and mindfulness interventions have been shown to be effective in reducing fatigue symptoms, we investigated the efficacy of a six-week Argentine tango program. [...] Read more.
Background: Persistent impairments of quality of life—in particular, cancer-associated fatigue—are a major limitation for breast cancer survivors. As physical activity and mindfulness interventions have been shown to be effective in reducing fatigue symptoms, we investigated the efficacy of a six-week Argentine tango program. Methods: A randomized controlled trial was conducted with 60 breast cancer survivors diagnosed with stage I-III tumors 12–48 months prior to study enrollment and who had increased symptoms of fatigue. The participants were randomly assigned with a 1:1 allocation to either the tango or the waiting group. The treatment consisted of six weeks of supervised weekly one-hour tango group-sessions. Self-reported fatigue and further quality of life parameters were assessed at baseline and six weeks post-baseline. Longitudinal changes, correlations, Cohen’s D (d) effect sizes, and association factors were also calculated. Results: Superiority of the tango intervention over the waiting list control was found in terms of improvement in fatigue (d = −0.64; 95%CI, −1.2 to −0.08; p = 0.03), especially cognitive fatigue. In addition, a superiority of the tango intervention over the waiting list was found in the improvement of diarrhea (d = −0.69; 95%CI, −1.25 to −0.13; p = 0.02). A pooled pre-post analysis of the 50 participants completing the six-week tango program revealed a close to 10% improvement of fatigue (p = 0.0003), insomnia (p = 0.008) and further quality of life outcomes. Adjusted multivariate linear regression analyses revealed the greatest improvements for participants who were more active in sports. In particular, survivors who received endocrine therapies, were obese, or had no prior dance experience seemed to especially benefit from the tango program. Conclusions: This randomized controlled trial demonstrated that a six-week Argentine tango program improves fatigue in breast cancer survivors. Further trials are warranted to determine whether such improvements lead to better long-term clinical outcomes. Trial registration: trial registration number DRKS00021601. Retrospectively registered on 21 August 2020. Full article
(This article belongs to the Special Issue Breast Cancer Survivors and Supportive Therapies)
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