Journal Description
Cancers
Cancers
is a peer-reviewed, open access journal of oncology, published semimonthly online by MDPI. The Irish Association for Cancer Research (IACR), Spanish Association for Cancer Research (ASEICA), Biomedical Research Centre (CIBM), British Neuro-Oncology Society (BNOS) and Spanish Group for Cancer Immuno-Biotherapy (GÉTICA) are affiliated with Cancers and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Oncology) / CiteScore - Q1 (Oncology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 17.9 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Sections: published in 18 topical sections.
- Companion journals for Cancers include: Radiation and Onco.
Impact Factor:
5.2 (2022);
5-Year Impact Factor:
5.6 (2022)
Latest Articles
Pediatric Diffuse Midline Glioma H3K27-Altered: From Developmental Origins to Therapeutic Challenges
Cancers 2024, 16(10), 1814; https://doi.org/10.3390/cancers16101814 (registering DOI) - 10 May 2024
Abstract
Diffuse intrinsic pontine glioma (DIPG), now referred to as diffuse midline glioma (DMG), is a highly aggressive pediatric cancer primarily affecting children aged 4 to 9 years old. Despite the research and clinical trials conducted to identify a possible treatment for DIPG, no
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Diffuse intrinsic pontine glioma (DIPG), now referred to as diffuse midline glioma (DMG), is a highly aggressive pediatric cancer primarily affecting children aged 4 to 9 years old. Despite the research and clinical trials conducted to identify a possible treatment for DIPG, no effective drug is currently available. These tumors often affect deep midline brain structures in young children, suggesting a connection to early brain development’s epigenetic regulation targets, possibly affecting neural progenitor functions and differentiation. The H3K27M mutation is a known DIPG trigger, but the exact mechanisms beyond epigenetic regulation remain unclear. After thoroughly examining the available literature, we found that over 85% of DIPG tumors contain a somatic missense mutation, K27M, in genes encoding histone H3.3 and H3.1, leading to abnormal gene expression that drives tumor growth and spread. This mutation impacts crucial brain development processes, including the epithelial–mesenchymal transition (EMT) pathway, and may explain differences between H3K27M and non-K27M pediatric gliomas. Effects on stem cells show increased proliferation and disrupted differentiation. The genomic organization of H3 gene family members in the developing brain has revealed variations in their expression patterns. All these observations suggest a need for global efforts to understand developmental origins and potential treatments.
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(This article belongs to the Topic From Basic Research to a Clinical Perspective in Oncology)
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Resection Ratios and Tumor Eccentricity in Breast-Conserving Surgery Specimens for Surgical Accuracy Assessment
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Dinusha Veluponnar, Behdad Dashtbozorg, Marcos Da Silva Guimaraes, Marie-Jeanne T. F. D. Vrancken Peeters, Lisanne L. de Boer and Theo J. M. Ruers
Cancers 2024, 16(10), 1813; https://doi.org/10.3390/cancers16101813 (registering DOI) - 9 May 2024
Abstract
This study aims to evaluate several defined specimen parameters that would allow to determine the surgical accuracy of breast-conserving surgeries (BCS) in a representative population of patients. These specimen parameters could be used to compare surgical accuracy when using novel technologies for intra-operative
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This study aims to evaluate several defined specimen parameters that would allow to determine the surgical accuracy of breast-conserving surgeries (BCS) in a representative population of patients. These specimen parameters could be used to compare surgical accuracy when using novel technologies for intra-operative BCS guidance in the future. Different specimen parameters were determined among 100 BCS patients, including the ratio of specimen volume to tumor volume (resection ratio) with different optimal margin widths (0 mm, 1 mm, 2 mm, and 10 mm). Furthermore, the tumor eccentricity [maximum tumor-margin distance − minimum tumor-margin distance] and the relative tumor eccentricity [tumor eccentricity ÷ pathological tumor diameter] were determined. Different patient subgroups were compared using Wilcoxon rank sum tests. When using a surgical margin width of 0 mm, 1 mm, 2 mm, and 10 mm, on average, 19.16 (IQR 44.36), 9.94 (IQR 18.09), 6.06 (IQR 9.69) and 1.35 (IQR 1.78) times the ideal resection volume was excised, respectively. The median tumor eccentricity among the entire patient population was 11.29 mm (SD = 3.99) and the median relative tumor eccentricity was 0.66 (SD = 2.22). Resection ratios based on different optimal margin widths (0 mm, 1 mm, 2 mm, and 10 mm) and the (relative) tumor eccentricity could be valuable outcome measures to evaluate the surgical accuracy of novel technologies for intra-operative BCS guidance.
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(This article belongs to the Special Issue Recent Advances and Challenges in Breast Cancer Surgery)
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Zebrafish Avatars: Toward Functional Precision Medicine in Low-Grade Serous Ovarian Cancer
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Charlotte Fieuws, Jan Willem Bek, Bram Parton, Elyne De Neef, Olivier De Wever, Milena Hoorne, Marta F. Estrada, Jo Van Dorpe, Hannelore Denys, Koen Van de Vijver and Kathleen B. M. Claes
Cancers 2024, 16(10), 1812; https://doi.org/10.3390/cancers16101812 - 9 May 2024
Abstract
Ovarian cancer (OC) is an umbrella term for cancerous malignancies affecting the ovaries, yet treatment options for all subtypes are predominantly derived from high-grade serous ovarian cancer, the largest subgroup. The concept of "functional precision medicine" involves gaining personalized insights on therapy choice,
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Ovarian cancer (OC) is an umbrella term for cancerous malignancies affecting the ovaries, yet treatment options for all subtypes are predominantly derived from high-grade serous ovarian cancer, the largest subgroup. The concept of "functional precision medicine" involves gaining personalized insights on therapy choice, based on direct exposure of patient tissues to drugs. This especially holds promise for rare subtypes like low-grade serous ovarian cancer (LGSOC). This study aims to establish an in vivo model for LGSOC using zebrafish embryos, comparing treatment responses previously observed in mouse PDX models, cell lines and 3D tumor models. To address this goal, a well-characterized patient-derived LGSOC cell line with the KRAS mutation c.35 G > T (p.(Gly12Val)) was used. Fluorescently labeled tumor cells were injected into the perivitelline space of 2 days’ post-fertilization zebrafish embryos. At 1 day post-injection, xenografts were assessed for tumor size, followed by random allocation into treatment groups with trametinib, luminespib and trametinib + luminespib. Subsequently, xenografts were euthanized and analyzed for apoptosis and proliferation by confocal microscopy. Tumor cells formed compact tumor masses (n = 84) in vivo, with clear Ki67 staining, indicating proliferation. Zebrafish xenografts exhibited sensitivity to trametinib and luminespib, individually or combined, within a two-week period, establishing them as a rapid and complementary tool to existing in vitro and in vivo models for evaluating targeted therapies in LGSOC.
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(This article belongs to the Special Issue Advances in Ovarian Cancer Research and Treatment)
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Open AccessArticle
Impact of Nutritional Status on Neutrophil-to-Lymphocyte Ratio as a Predictor of Efficacy and Adverse Events of Immune Check-Point Inhibitors
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Masahiko Sue, Yasuto Takeuchi, Shoichiro Hirata, Akinobu Takaki and Motoyuki Otsuka
Cancers 2024, 16(10), 1811; https://doi.org/10.3390/cancers16101811 - 9 May 2024
Abstract
The neutrophil -to-lymphocyte ratio (NLR) is useful for predicting the effectiveness of treatment with immune checkpoint inhibitors (ICIs) and immune-related adverse events (irAEs). Because a growing body of evidence has recently shown that the number of lymphocytes that comprise NLR fluctuates according to
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The neutrophil -to-lymphocyte ratio (NLR) is useful for predicting the effectiveness of treatment with immune checkpoint inhibitors (ICIs) and immune-related adverse events (irAEs). Because a growing body of evidence has recently shown that the number of lymphocytes that comprise NLR fluctuates according to nutritional status, this study examined whether the usefulness of NLR varies in ICI treatment due to changes in nutritional status. A retrospective analysis was performed on 1234 patients who received ICI treatment for malignant tumors at our hospital. Progression-free survival (PFS) was significantly prolonged in patients with NLR < 4. Multivariate analysis revealed that the factors associated with the occurrence of irAE were NLR < 4 and the use of ipilimumab. However, when limited to cases with serum albumin levels <3.8 g/dL, lymphocyte counts significantly decreased, and the associations between NLR and PFS and between NLR and irAE occurrence disappeared. In contrast, when limited to the cases with serum albumin levels ≥3.8 g/dL, the associations remained, with significantly prolonged PFS and significantly increased irAE occurrence at NLR < 4. NLR may be a good predictive tool for PFS and irAE occurrence during ICI treatment when a good nutritional status is maintained.
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(This article belongs to the Special Issue Immune-Related Adverse Events in Patients with Cancer: From Bench to Bedside)
Open AccessArticle
Prediction of Mismatch Repair Status in Endometrial Cancer from Histological Slide Images Using Various Deep Learning-Based Algorithms
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Mina Umemoto, Tasuku Mariya, Yuta Nambu, Mai Nagata, Toshihiro Horimai, Shintaro Sugita, Takayuki Kanaseki, Yuka Takenaka, Shota Shinkai, Motoki Matsuura, Masahiro Iwasaki, Yoshihiko Hirohashi, Tadashi Hasegawa, Toshihiko Torigoe, Yuichi Fujino and Tsuyoshi Saito
Cancers 2024, 16(10), 1810; https://doi.org/10.3390/cancers16101810 - 9 May 2024
Abstract
The application of deep learning algorithms to predict the molecular profiles of various cancers from digital images of hematoxylin and eosin (H&E)-stained slides has been reported in recent years, mainly for gastric and colon cancers. In this study, we investigated the potential use
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The application of deep learning algorithms to predict the molecular profiles of various cancers from digital images of hematoxylin and eosin (H&E)-stained slides has been reported in recent years, mainly for gastric and colon cancers. In this study, we investigated the potential use of H&E-stained endometrial cancer slide images to predict the associated mismatch repair (MMR) status. H&E-stained slide images were collected from 127 cases of the primary lesion of endometrial cancer. After digitization using a Nanozoomer virtual slide scanner (Hamamatsu Photonics), we segmented the scanned images into 5397 tiles of 512 × 512 pixels. The MMR proteins (PMS2, MSH6) were immunohistochemically stained, classified into MMR proficient/deficient, and annotated for each case and tile. We trained several neural networks, including convolutional and attention-based networks, using tiles annotated with the MMR status. Among the tested networks, ResNet50 exhibited the highest area under the receiver operating characteristic curve (AUROC) of 0.91 for predicting the MMR status. The constructed prediction algorithm may be applicable to other molecular profiles and useful for pre-screening before implementing other, more costly genetic profiling tests.
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(This article belongs to the Special Issue Novel Approaches to Machine Learning and Artificial Intelligence in Cancer Research and Care)
Open AccessReview
Catalyzing Precision Medicine: Artificial Intelligence Advancements in Prostate Cancer Diagnosis and Management
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Ali Talyshinskii, B. M. Zeeshan Hameed, Prajwal P. Ravinder, Nithesh Naik, Princy Randhawa, Milap Shah, Bhavan Prasad Rai, Theodoros Tokas and Bhaskar K. Somani
Cancers 2024, 16(10), 1809; https://doi.org/10.3390/cancers16101809 - 9 May 2024
Abstract
Background: The aim was to analyze the current state of deep learning (DL)-based prostate cancer (PCa) diagnosis with a focus on magnetic resonance (MR) prostate reconstruction; PCa detection/stratification/reconstruction; positron emission tomography/computed tomography (PET/CT); androgen deprivation therapy (ADT); prostate biopsy; associated challenges and their
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Background: The aim was to analyze the current state of deep learning (DL)-based prostate cancer (PCa) diagnosis with a focus on magnetic resonance (MR) prostate reconstruction; PCa detection/stratification/reconstruction; positron emission tomography/computed tomography (PET/CT); androgen deprivation therapy (ADT); prostate biopsy; associated challenges and their clinical implications. Methods: A search of the PubMed database was conducted based on the inclusion and exclusion criteria for the use of DL methods within the abovementioned areas. Results: A total of 784 articles were found, of which, 64 were included. Reconstruction of the prostate, the detection and stratification of prostate cancer, the reconstruction of prostate cancer, and diagnosis on PET/CT, ADT, and biopsy were analyzed in 21, 22, 6, 7, 2, and 6 studies, respectively. Among studies describing DL use for MR-based purposes, datasets with magnetic field power of 3 T, 1.5 T, and 3/1.5 T were used in 18/19/5, 0/1/0, and 3/2/1 studies, respectively, of 6/7 studies analyzing DL for PET/CT diagnosis which used data from a single institution. Among the radiotracers, [68Ga]Ga-PSMA-11, [18F]DCFPyl, and [18F]PSMA-1007 were used in 5, 1, and 1 study, respectively. Only two studies that analyzed DL in the context of DT met the inclusion criteria. Both were performed with a single-institution dataset with only manual labeling of training data. Three studies, each analyzing DL for prostate biopsy, were performed with single- and multi-institutional datasets. TeUS, TRUS, and MRI were used as input modalities in two, three, and one study, respectively. Conclusion: DL models in prostate cancer diagnosis show promise but are not yet ready for clinical use due to variability in methods, labels, and evaluation criteria. Conducting additional research while acknowledging all the limitations outlined is crucial for reinforcing the utility and effectiveness of DL-based models in clinical settings.
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(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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Driver Mutations in Pancreatic Cancer and Opportunities for Targeted Therapy
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Olamide T. Olaoba, Temitope I. Adelusi, Ming Yang, Tessa Maidens, Eric T. Kimchi, Kevin F. Staveley-O’Carroll and Guangfu Li
Cancers 2024, 16(10), 1808; https://doi.org/10.3390/cancers16101808 - 9 May 2024
Abstract
Pancreatic cancer is the sixth leading cause of cancer-related mortality globally. As the most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) represents up to 95% of all pancreatic cancer cases, accounting for more than 300,000 deaths annually. Due to the lack
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Pancreatic cancer is the sixth leading cause of cancer-related mortality globally. As the most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) represents up to 95% of all pancreatic cancer cases, accounting for more than 300,000 deaths annually. Due to the lack of early diagnoses and the high refractory response to the currently available treatments, PDAC has a very poor prognosis, with a 5-year overall survival rate of less than 10%. Targeted therapy and immunotherapy are highly effective and have been used for the treatment of many types of cancer; however, they offer limited benefits in pancreatic cancer patients due to tumor-intrinsic and extrinsic factors that culminate in drug resistance. The identification of key factors responsible for PDAC growth and resistance to different treatments is highly valuable in developing new effective therapeutic strategies. In this review, we discuss some molecules which promote PDAC initiation and progression, and their potential as targets for PDAC treatment. We also evaluate the challenges associated with patient outcomes in clinical trials and implications for future research.
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(This article belongs to the Section Cancer Immunology and Immunotherapy)
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Systemic DNA Damage and Repair Activity Vary by Race in Breast Cancer Survivors
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Shraddha Divekar, Ryan Kritzer, Haokai Shu, Keval Thakkar, Jennifer Hicks, Mary G. Mills, Kepher Makambi, Chiranjeev Dash and Rabindra Roy
Cancers 2024, 16(10), 1807; https://doi.org/10.3390/cancers16101807 - 9 May 2024
Abstract
Non-Hispanic Black breast cancer survivors have poorer outcomes and higher mortality rates than White survivors, but systemic biological mechanisms underlying these disparities are unclear. We used circulating leukocytes as a surrogate for measuring systemic mechanisms, which might be different from processes in the
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Non-Hispanic Black breast cancer survivors have poorer outcomes and higher mortality rates than White survivors, but systemic biological mechanisms underlying these disparities are unclear. We used circulating leukocytes as a surrogate for measuring systemic mechanisms, which might be different from processes in the target tissue (e.g., breast). We investigated race-based differences in DNA damage and repair, using a novel CometChip assay, in circulating leukocytes from breast cancer survivors who had completed primary cancer therapy and were cancer free. We observed novel race-based differences in systemic DNA damage and repair activity in cancer survivors, but not in cells from healthy volunteers. Basal DNA damage in leukocytes was higher in White survivors, but Black survivors showed a much higher induction after bleomycin treatment. Double-strand break repair activity was also significantly different between the races, with cells from White survivors showing more sustained repair activity compared to Black leukocytes. These results suggest that cancer and cancer therapy might have long-lasting effects on systemic DNA damage and repair mechanisms that differ in White survivors and Black survivors. Findings from our preliminary study in non-cancer cells (circulating leukocytes) suggest systemic effects beyond the target site, with implications for accelerated aging-related cancer survivorship disparities.
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(This article belongs to the Collection Advances in Cancer Disparities)
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Gut Microbiota Are a Novel Source of Biomarkers for Immunotherapy in Non-Small-Cell Lung Cancer (NSCLC)
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Teresa Del Giudice, Nicoletta Staropoli, Pierfrancesco Tassone, Pierosandro Tagliaferri and Vito Barbieri
Cancers 2024, 16(10), 1806; https://doi.org/10.3390/cancers16101806 - 9 May 2024
Abstract
Despite the recent availability of immune checkpoint inhibitors, not all patients affected by Non-Small-Cell Lung Cancer (NSCLC) benefit from immunotherapy. The reason for this variability relies on a variety of factors which may allow for the identification of novel biomarkers. Presently, a variety
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Despite the recent availability of immune checkpoint inhibitors, not all patients affected by Non-Small-Cell Lung Cancer (NSCLC) benefit from immunotherapy. The reason for this variability relies on a variety of factors which may allow for the identification of novel biomarkers. Presently, a variety of biomarkers are under investigation, including the PD1/PDL1 axis, the tumor mutational burden, and the microbiota. The latter is made by all the bacteria and other microorganisms hosted in our body. The gut microbiota is the most represented and has been involved in different physiological and pathological events, including cancer. In this light, it appears that all conditions modifying the gut microbiota can influence cancer, its treatment, and its treatment-related toxicities. The aim of this review is to analyze all the conditions influencing the gut microbiota and, therefore, affecting the response to immunotherapy, iRAEs, and their management in NSCLC patients. The investigation of the landscape of these biological events can allow for novel insights into the optimal management of NSCLC immunotherapy.
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(This article belongs to the Special Issue Novel Biomarkers in Non-small Cell Lung Cancer (NSCLC))
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Schlafens: Emerging Therapeutic Targets
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Ricardo E. Perez, Frank Eckerdt and Leonidas C. Platanias
Cancers 2024, 16(10), 1805; https://doi.org/10.3390/cancers16101805 - 9 May 2024
Abstract
The interferon (IFN) family of immunomodulatory cytokines has been a focus of cancer research for over 50 years with direct and indirect implications in cancer therapy due to their properties to inhibit malignant cell proliferation and modulate immune responses. Among the transcriptional targets
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The interferon (IFN) family of immunomodulatory cytokines has been a focus of cancer research for over 50 years with direct and indirect implications in cancer therapy due to their properties to inhibit malignant cell proliferation and modulate immune responses. Among the transcriptional targets of the IFNs is a family of genes referred to as Schlafens. The products of these genes, Schlafen proteins, exert important roles in modulating cellular proliferation, differentiation, immune responses, viral replication, and chemosensitivity of malignant cells. Studies have demonstrated that abnormal expression of various Schlafens contributes to the pathophysiology of various cancers. Schlafens are now emerging as promising biomarkers and potentially attractive targets for drug development in cancer research. Here, we highlight research suggesting the use of Schlafens as cancer biomarkers and the rationale for the development of specific drugs targeting Schlafen proteins.
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(This article belongs to the Section Cancer Therapy)
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Open AccessSystematic Review
Reconstruction of Partial Hypopharyngeal Defects following Total Laryngectomy: A Systematic Review and Meta-Analysis
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Anthony M. Tonsbeek, Roxy Leidelmeijer, Caroline A. Hundepool, Liron S. Duraku, Mark J. W. Van der Oest, Aniel Sewnaik and Marc A. M. Mureau
Cancers 2024, 16(10), 1804; https://doi.org/10.3390/cancers16101804 - 8 May 2024
Abstract
Background: Various operative techniques exist to reconstruct partial hypopharyngeal defects following total laryngectomy. The current study aimed to investigate and compare complications and functional results following commonly used reconstructive techniques. Methods: A systematic review and meta-analysis were performed using studies that investigated outcomes
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Background: Various operative techniques exist to reconstruct partial hypopharyngeal defects following total laryngectomy. The current study aimed to investigate and compare complications and functional results following commonly used reconstructive techniques. Methods: A systematic review and meta-analysis were performed using studies that investigated outcomes after the reconstruction of a partial hypopharyngeal defect. The outcomes of interest were fistulas, strictures, flap failure, swallowing function and postoperative speech. Results: Of the 4035 studies identified, 23 were included in this review. Four common reconstructive techniques were reported, with a total of 794 patients: (1) pectoralis major myocutaneous and (2) myofascial flap, (3) anterolateral thigh free flap and (4) radial forearm free flap. Fistulas occurred significantly more often than pectoralis major myocutaneous flaps (34%, 95% CI 23–47%) compared with other flaps (p < 0.001). No significant differences in the rates of strictures or flap failure were observed. Pectoralis major myofascial flaps were non-inferior to free-flap reconstructions. Insufficient data were available to assess speech results between flap types. Conclusion: Pectoralis myocutaneous flaps should not be the preferred method of reconstruction for most patients, considering their significantly higher rate of fistulas. In contrast, pectoralis major myofascial flaps yield promising results compared to free-flap reconstructions, warranting further investigation.
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(This article belongs to the Special Issue Advances in Surgery of Head and Neck Squamous Cell Carcinoma)
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Open AccessArticle
Liver Transplantation from Elderly Donors (≥85 Years Old)
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Pierluigi Romano, Luis Cano, Daniel Pietrasz, Nassiba Beghdadi, Marc-Antoine Allard, Chady Salloum, Frédérique Blandin, Oriana Ciacio, Gabriella Pittau, René Adam, Daniel Azoulay, Antonio Sa Cunha, Eric Vibert, Luciano De Carlis, Alessandro Vitale, Umberto Cillo, Daniel Cherqui and Nicolas Golse
Cancers 2024, 16(10), 1803; https://doi.org/10.3390/cancers16101803 - 8 May 2024
Abstract
Background: Despite the ongoing trend of increasing donor ages in liver transplantation (LT) setting, a notable gap persists in the availability of comprehensive guidelines for the utilization of organs from elderly donors. This study aimed to evaluate the viability of livers grafts from
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Background: Despite the ongoing trend of increasing donor ages in liver transplantation (LT) setting, a notable gap persists in the availability of comprehensive guidelines for the utilization of organs from elderly donors. This study aimed to evaluate the viability of livers grafts from donors aged ≥85 years and report the post-LT outcomes compared with those from “ideal” donors under 40 years old. Methods: Conducted retrospectively at a single center from 2005 to 2023, this study compared outcomes of LTs from donors aged ≥85 y/o and ≤40 y/o, with the propensity score matching to the recipient’s gender, age, BMI, MELD score, redo-LT, LT indication, and cause of donor death. Results: A total of 76 patients received grafts from donors ≥85 y/o and were compared to 349 liver grafts from donors ≤40 y/o. Prior to PSM, the 5-year overall survival was 63% for the elderly group and 77% for the young group (p = 0.002). After PSM, the 5-year overall survival was 63% and 73% (p = 0.1). A nomogram, developed at the time of graft acceptance and including HCC features, predicted 10-year survival after LT using a graft from a donor aged ≥85. Conclusions: In the context of organ scarcity, elderly donors emerge as a partial solution. Nonetheless, without proper selection, LT using very elderly donors yields inferior long-term outcomes compared to transplantation from very young donors ≤40 y/o. The resulting nomogram based on pre-transplant criteria allows for the optimization of elderly donor/recipient matching to achieve satisfactory long-term results, in addition to traditional matching methods.
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(This article belongs to the Special Issue Advances and Future Developments in Liver Transplantation for Cancers)
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Real-World Safety and Outcome of First-Line Pembrolizumab Monotherapy for Metastatic NSCLC with PDL-1 Expression ≥ 50%: A National Italian Multicentric Cohort (“PEMBROREAL” Study)
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Alessandro Cafaro, Flavia Foca, Oriana Nanni, Marco Chiumente, Marina Coppola, Alberto Russi, Elena Svegliati, Paolo Baldo, Sabrina Orzetti, Fiorenza Enrico, Federico Foglio, Davide Pinnavaia, Vito Ladisa, Claudia Lauria Pantano, Rosa Lerose, Patrizia Nardulli, Simona Ferraiuolo, Piera Maiolino, Immacolata De Stasio, Federica Gradellini, Anna Rita Gasbarro, Rossella Santeramo, Gisella Carrucciu, Riccardo Provasi, Mario Cirino, Paola Cristina Cappelletto, Elisabetta Fonzi, Alessandra Pasqualini, Stefano Vecchia, Marianna Veraldi, Adele Emanuela De Francesco, Lucio Crinò, Angelo Delmonte and Carla Masiniadd
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Cancers 2024, 16(10), 1802; https://doi.org/10.3390/cancers16101802 - 8 May 2024
Abstract
Results from the phase III Keynote-024 clinical trial established pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR, and ALK wild-type tumors. However, given the differences between patients treated in routine
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Results from the phase III Keynote-024 clinical trial established pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR, and ALK wild-type tumors. However, given the differences between patients treated in routine clinical practice and those treated in a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-ups, we designed an observational retrospective study of patients with metastatic NSCLC who were treated with pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were PFS and OS, determined using the Kaplan–Meier method. Response and safety were also evaluated. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6–10.0) and 25.5 months (95% CI: 21.8–31.6), respectively. We also found that ECOG PS, PD-L1 expression, and habitual smoking were prognostic factors for PFS, while age, sex, ECOG PS, habitual smoking and histology had an impact on OS. Multivariable analysis confirms the prognostic role of PD-L1 for PFS and of ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of pembrolizumab in the first-line setting, as well as a safety profile consistent with the results of Keynote-024. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.
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(This article belongs to the Special Issue Evidence from the Real World Provides New Insights into the Evolving Landscape of Cancer Immunotherapy)
Open AccessReview
Current Status and Future Perspectives of Antibody–Drug Conjugates in Hormone Receptor-Positive Breast Cancer
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Maria Grammoustianou, Foteinos-Ioannis Dimitrakopoulos and Angelos Koutras
Cancers 2024, 16(10), 1801; https://doi.org/10.3390/cancers16101801 - 8 May 2024
Abstract
Breast cancer is the most common cancer type in women. The vast majority of breast cancer patients have hormone receptor-positive (HR+) tumors. In advanced HR+ breast cancer, the combination of endocrine therapy with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors is considered the standard of
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Breast cancer is the most common cancer type in women. The vast majority of breast cancer patients have hormone receptor-positive (HR+) tumors. In advanced HR+ breast cancer, the combination of endocrine therapy with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors is considered the standard of care in the front-line setting. Nevertheless, resistance to hormonal therapy and CDK4/6 inhibitors eventually occurs, leading to progression of the disease. Antibody–drug conjugates (ADCs) comprise a promising therapeutic choice with significant efficacy in patients with HR+ breast cancer, which is resistant to endocrine treatment. ADCs typically consist of a cytotoxic payload attached by a linker to a monoclonal antibody that targets a specific tumor-associated antigen, offering the advantage of a more selective delivery of chemotherapy to cancer cells. In this review, we focus on the ADC mechanisms of action, their toxicity profile and therapeutic uses as well as on related biomarkers and future perspectives in advanced HR+ breast cancer.
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(This article belongs to the Special Issue 2nd Edition: Estrogen Receptor-Positive (ER+) Breast Cancers)
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Cutaneous Squamous Cell Carcinoma: An Updated Review
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Rina Jiang, Mike Fritz and Syril Keena T. Que
Cancers 2024, 16(10), 1800; https://doi.org/10.3390/cancers16101800 - 8 May 2024
Abstract
Representing the second most common skin cancer, the incidence and disease burden of cutaneous squamous cell carcinoma (cSCC) continues to increase. Surgical excision of the primary site effectively cures the majority of cSCC cases. However, an aggressive subset of cSCC persists with clinicopathological
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Representing the second most common skin cancer, the incidence and disease burden of cutaneous squamous cell carcinoma (cSCC) continues to increase. Surgical excision of the primary site effectively cures the majority of cSCC cases. However, an aggressive subset of cSCC persists with clinicopathological features that are indicative of higher recurrence, metastasis, and mortality risks. Acceleration of these features is driven by a combination of genetic and environmental factors. The past several years have seen remarkable progress in shaping the treatment landscape for advanced cSCC. Risk stratification and clinical management is a top priority. This review provides an overview of the current perspectives on cSCC with a focus on staging, treatment, and maintenance strategies, along with future research directions.
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(This article belongs to the Special Issue Recent Advances in Skin Cancers)
Open AccessReview
CXCR4: From Signaling to Clinical Applications in Neuroendocrine Neoplasms
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David Sanchis-Pascual, María Isabel Del Olmo-García, Stefan Prado-Wohlwend, Carlos Zac-Romero, Ángel Segura Huerta, Javier Hernández-Gil, Luis Martí-Bonmatí and Juan Francisco Merino-Torres
Cancers 2024, 16(10), 1799; https://doi.org/10.3390/cancers16101799 - 8 May 2024
Abstract
There are several well-described molecular mechanisms that influence cell growth and are related to the development of cancer. Chemokines constitute a fundamental element that is not only involved in local growth but also affects angiogenesis, tumor spread, and metastatic disease. Among them, the
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There are several well-described molecular mechanisms that influence cell growth and are related to the development of cancer. Chemokines constitute a fundamental element that is not only involved in local growth but also affects angiogenesis, tumor spread, and metastatic disease. Among them, the C-X-C motif chemokine ligand 12 (CXCL12) and its specific receptor the chemokine C-X-C motif receptor 4 (CXCR4) have been widely studied. The overexpression in cell membranes of CXCR4 has been shown to be associated with the development of different kinds of histological malignancies, such as adenocarcinomas, epidermoid carcinomas, mesenchymal tumors, or neuroendocrine neoplasms (NENs). The molecular synapsis between CXCL12 and CXCR4 leads to the interaction of G proteins and the activation of different intracellular signaling pathways in both gastroenteropancreatic (GEP) and bronchopulmonary (BP) NENs, conferring greater capacity for locoregional aggressiveness, the epithelial–mesenchymal transition (EMT), and the appearance of metastases. Therefore, it has been hypothesized as to how to design tools that target this receptor. The aim of this review is to focus on current knowledge of the relationship between CXCR4 and NENs, with a special emphasis on diagnostic and therapeutic molecular targets.
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(This article belongs to the Special Issue Neuroendocrine Tumors: Clinical and Translational Research)
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Gene Expression Profile of Benign, Intermediate, and Malignant Spitz and Spitzoid Melanocytic Lesions
by
Alessio Giubellino, Yuyu He, Sarah A. Munro, Yan Zhou, Kyu Young Song, Jose A. Plaza, Carlos A. Torres-Cabala and Andrew C. Nelson
Cancers 2024, 16(10), 1798; https://doi.org/10.3390/cancers16101798 - 8 May 2024
Abstract
Spitz and Spitzoid lesions represent one of the most challenging melanocytic neoplasms in dermatopathology. Nosologic classification has been more recently improved by the discovery of novel molecular drivers, particularly translocations. In the current study, we aimed to use an unbiased approach to explore
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Spitz and Spitzoid lesions represent one of the most challenging melanocytic neoplasms in dermatopathology. Nosologic classification has been more recently improved by the discovery of novel molecular drivers, particularly translocations. In the current study, we aimed to use an unbiased approach to explore the gene expression profile of a group of melanocytic Spitz and Spitzoid melanocytic lesions ranging from benign lesions to melanoma, including intermediate lesions such as SPARK nevi and atypical Spitz tumors/melanocytomas. Using unsupervised analysis of gene expression data, we found some distinct hierarchical clusters of lesions, including groups characterized by ALK and NTRK translocations. Few non-ALK translocated tumors demonstrated increased ALK expression, confirmed by immunohistochemistry. Spitz tumors with overlapping features of dysplastic nevi, so-called SPARK nevi, appear to have a common gene expression profile by hierarchical clustering. Finally, weighted gene correlation network analysis identified gene modules variably regulated in subtypes of these cases. Thus, gene expression profiling of Spitz and Spitzoid lesions represents a viable instrument for the characterization of these lesions.
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(This article belongs to the Special Issue Melanoma: Pathology and Translational Research)
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Effect of Tumor Regression Grade on Survival and Disease-Free Interval in Patients Operated on for Locally Advanced Rectal Cancer
by
Fernando Mendoza-Moreno, Manuel Díez-Alonso, Belén Matías-García, Enrique Ovejero-Merino, Cristina Vera-Mansilla, Ana Quiroga-Valcárcel, Alma Blázquez-Martín, Rubén Jiménez-Martín, Inmaculada Lasa-Unzúe, Miguel A. Ortega, Melchor Alvarez-Mon and Alberto Gutiérrez-Calvo
Cancers 2024, 16(10), 1797; https://doi.org/10.3390/cancers16101797 - 8 May 2024
Abstract
Introduction: Colorectal cancer is the fourth leading cause of cancer-related death in both men and women in our population. In this regard, rectal cancer accounts for more than half of colorectal cancer deaths, and its incidence is expected to increase in the coming
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Introduction: Colorectal cancer is the fourth leading cause of cancer-related death in both men and women in our population. In this regard, rectal cancer accounts for more than half of colorectal cancer deaths, and its incidence is expected to increase in the coming years. There have been significant changes in neoadjuvant therapy regimens, with promising results, as demonstrated by the recent RAPIDO and PRODIGE23 studies. Around 40% of patients diagnosed with locally advanced rectal cancer show some degree of response to neoadjuvant treatment, with complete tumor regression observed in up to one in five patients. Materials and Methods: Retrospective observational study. A total of 181 patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were analyzed. Clinical and pathological data were collected from the patients, including assessment of tumor regression through histopathological studies after surgery. The Mandard tumor regression grading system was used to categorize tumor response into different grades. Results: The results showed a significant association between the degree of tumor regression and several important clinical outcomes. Specifically, patients with higher tumor regression had significantly better disease-free survival than those with less regression (p = 0.004). In addition, tumor regression was also correlated with the incidence of local recurrence (p = 0.018) and distant metastasis (p = 0.032). These associations suggest that tumor responsiveness to neoadjuvant therapy may influence the long-term progression of the disease. Regarding tumor deposits and the presence of lymphadenopathy, these factors were also found to be significantly associated with clinical outcomes. Patients with tumor deposits had a higher incidence of local recurrence (p = 0.025) and distant metastases (p = 0.041), while the presence of lymphadenopathy increased the risk of local recurrence (p = 0.013). These findings highlight the importance of evaluating not only tumor regression but also other pathological markers to predict prognosis and guide clinical management. Conclusions: The degree of tumor regression was not an independent predictor of survival compared to other variables such as nodal stage and presence of tumor deposits. This indicates that while tumor regression is an important factor, other elements also play a crucial role in determining the prognosis of patients with locally advanced rectal cancer. This study provides additional evidence for the importance of tumor regression, tumor deposits, and lymphadenopathy as predictors of clinical outcomes in patients with rectal cancer treated with neoadjuvant chemoradiotherapy.
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(This article belongs to the Special Issue The Surgical Management of Colorectal Cancer)
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Pepsinogen C Interacts with IQGAP1 to Inhibit the Metastasis of Gastric Cancer Cells by Suppressing Rho-GTPase Pathway
by
Hanxi Ding, Yingnan Liu, Xiaodong Lu, Aoran Liu, Qian Xu and Yuan Yuan
Cancers 2024, 16(10), 1796; https://doi.org/10.3390/cancers16101796 - 8 May 2024
Abstract
Aim: This study systematically explored the biological effects and mechanisms of PGC on gastric cancer (GC) cells in vitro and in vivo. Method: The critical biological roles of PGC in GC were assessed via EdU staining, Hoechst staining, flow cytometry, mouse models, CCK-8,
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Aim: This study systematically explored the biological effects and mechanisms of PGC on gastric cancer (GC) cells in vitro and in vivo. Method: The critical biological roles of PGC in GC were assessed via EdU staining, Hoechst staining, flow cytometry, mouse models, CCK-8, wound healing, transwell, and sphere-forming assays. The interaction study with IQ-domain GTPase-activating protein 1 (IQGAP1) was used by Liquid chromatography-mass spectrometry co-immunoprecipitation, immunofluorescence staining, CHX-chase assay, MG132 assay, and qRT-PCR. Results: PGC inhibited the proliferation, viability, epithelial–mesenchymal transition, migration, invasion, and stemness of GC cells and promoted GC cell differentiation. PGC suppressed subcutaneous tumor growth and peritoneal dissemination in vivo. The interaction study found PGC inhibits GC cell migration and invasion by downregulating IQGAP1 protein and IQGAP1-mediated Rho-GTPase signaling suppression. In addition, PGC disrupts the stability of the IQGAP1 protein, promoting its degradation and significantly shortening its half-life. Moreover, the expression levels of PGC and IQGAP1 in GC tissues were significantly negatively correlated. Conclusion: PGC may act as a tumor suppressor in the development and metastasis of GC. PGC can downregulate its interacting protein IQGAP1 and inhibit the Rho-GTPase pathway, thereby participating in the inhibition of GC cell migration and invasion.
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(This article belongs to the Section Molecular Cancer Biology)
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Exploring the Immunomodulatory Potential of Pancreatic Cancer-Derived Extracellular Vesicles through Proteomic and Functional Analyses
by
Anna Piro, Maria Concetta Cufaro, Paola Lanuti, Davide Brocco, Laura De Lellis, Rosalba Florio, Serena Pilato, Sara Pagotto, Simone De Fabritiis, Simone Vespa, Giulia Catitti, Fabio Verginelli, Pasquale Simeone, Damiana Pieragostino, Piero Del Boccio, Antonella Fontana, Antonino Grassadonia, Mauro Di Ianni, Alessandro Cama and Serena Veschi
Cancers 2024, 16(10), 1795; https://doi.org/10.3390/cancers16101795 - 8 May 2024
Abstract
Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicle (EV) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by
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Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicle (EV) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, Western blot (WB), nanoparticle tracking analysis, and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs, followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. The proteomics of lymphocytes sorted from EV-treated or untreated PBMCs was performed, and the IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by the proteomic analysis were connected in a single functional network (p = 1 × 10−16) and were involved in the “Immune System” (FDR: 1.10 × 10−24 and 3.69 × 10−19, respectively). Interestingly, the treatment of healthy donor-derived PBMCs with Capan-2 EVs but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. The proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among the major upstream regulators, as confirmed by ELISA. The proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune responses, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.
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(This article belongs to the Section Molecular Cancer Biology)
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