Cancers

21 pages, 2757 KiB

Open AccessArticle

Video-Assisted Mastectomy with Immediate Breast Reconstruction: First Clinical Experience and Outcomes in an Eastern European Medical Center

by Adrian Daniel Tulin, Daniela-Elena Ion, Adelaida Avino, Daniela-Elena Gheoca-Mutu, Abdalah Abu-Baker, Andrada-Elena Țigăran, Teodora Timofan, Ileana Ostafi, Cristian Radu Jecan and Laura Răducu

Cancers 2025, 17(13), 2267; https://doi.org/10.3390/cancers17132267 - 7 Jul 2025

Viewed by 316

Abstract

Background/Objectives: The aim of this case series is to evaluate the outcomes and safety of video-assisted mastectomy, illustrating the harmonious collaboration of oncologic and plastic surgery. This novel minimally invasive technique allows immediate prosthetic reconstruction and represents a cost-effective alternative to robotic breast [...] Read more.

Background/Objectives: The aim of this case series is to evaluate the outcomes and safety of video-assisted mastectomy, illustrating the harmonious collaboration of oncologic and plastic surgery. This novel minimally invasive technique allows immediate prosthetic reconstruction and represents a cost-effective alternative to robotic breast surgery. Methods: Video-assisted, single-port nipple-sparing mastectomies were performed in patients with small to medium-sized breasts, followed by immediate direct-to-implant reconstruction with either prepectoral or dual plane implant placement. The patients’ electronic medical records were analyzed, including demographic characteristics, operative times and histopathology reports. Results: A total of 18 patients underwent successful video-assisted mastectomy, without conversion to traditional open procedure. Fifteen of the operations were risk-reducing mastectomies. Twelve patients had complementary procedures performed concurrently on the previously operated contralateral breast (delayed reconstruction/expander-to-implant exchange). Moreover, three patients benefited from additional minimally invasive techniques during the same surgery (prophylactic laparoscopic hysterectomy). Immediate breast reconstruction with polyurethane or microtextured breast implants up to 450 cc was performed, with satisfactory aesthetic outcomes and no cancer recurrences at 6 to 12 months postoperative follow-up. Early complications included transient hypercapnia, areolar congestion and cellulitis. No skin necrosis or implant-related complications were reported. The most frequently encountered late issues were contour irregularities. Conclusions: Video-assisted mastectomy facilitates the safe removal of proven pathologic or healthy breast tissue with minimal damage to the breast’s skin envelope, facilitating single-stage breast reconstruction. Full article

(This article belongs to the Special Issue Recent Advances and Challenges in Breast Cancer Surgery: 2nd Edition)

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16 pages, 1965 KiB

Open AccessArticle

Establishment of an Orthotopic and Metastatic Colorectal Cancer Mouse Model Using a Tissue Adhesive-Based Implantation Method

by Sang Bong Lee, Hui-Jeon Jeon, Hoon Hyun and Yong Hyun Jeon

Cancers 2025, 17(13), 2266; https://doi.org/10.3390/cancers17132266 - 7 Jul 2025

Viewed by 435

Abstract

Background: To overcome the limitations of conventional CRC (colorectal cancer) mouse models in replicating metastasis and enabling efficient therapeutic evaluation, we developed a novel implantation method using tissue adhesive to establish reproducible orthotopic and metastatic tumors. Conventional models using injection or suturing techniques [...] Read more.

Background: To overcome the limitations of conventional CRC (colorectal cancer) mouse models in replicating metastasis and enabling efficient therapeutic evaluation, we developed a novel implantation method using tissue adhesive to establish reproducible orthotopic and metastatic tumors. Conventional models using injection or suturing techniques often suffer from technical complexity, inconsistent tumor establishment, and limited metastatic reliability. Methods: We developed and validated a novel orthotopic and metastatic CRC model utilizing tissue adhesive for tumor transplantation. Uniform tumor fragments derived from bioluminescent HCT116/Luc xenografts were affixed to the cecum of nude mice. Tumor growth and metastasis were monitored through bioluminescence imaging and confirmed by the results of histological analysis of metastatic lesions. The model’s utility for therapeutic testing was evaluated using MK801, an NMDA receptor antagonist. Results: The biological-based model demonstrated rapid and reproducible tumor implantation (<5 min), consistent primary tumor growth, and robust metastasis to the liver and lungs. The biological-based approach achieved 80% tumor engraftment (4/5), with consistent metastasis to the liver and lungs in all mice, compared with lower and variable metastasis rates in injection (0%, 0/5) and suturing (20%, 1/5) methods. MK801 treatment significantly suppressed both primary tumor growth and metastasis, validating the model’s suitability for preclinical drug evaluation. Conclusions: By enabling rapid, reproducible, and spontaneous formation of metastatic lesions using a minimally invasive tissue adhesive technique, our model represents a significant methodological advancement that supports high-throughput therapeutic screening and bridges the gap between experimental modeling and clinical relevance in colorectal cancer research. Full article

(This article belongs to the Special Issue Colorectal Cancer Liver Metastases)

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14 pages, 362 KiB

Open AccessReview

Recent Advances in Immunotherapy for Melanoma: Perspectives on the Development of Novel Treatments: A Mini Review

by Yusuke Muto, Taku Fujimura and Yoshihide Asano

Cancers 2025, 17(13), 2265; https://doi.org/10.3390/cancers17132265 - 7 Jul 2025

Viewed by 371

Abstract

It has been more than a decade since anti-PD-1 and anti-CTLA-4 antibodies were first introduced for the treatment of unresectable melanoma. The advent of these immunotherapies has dramatically transformed the treatment landscape. In recent years, anti-PD-1 antibodies have become the cornerstone of melanoma [...] Read more.

It has been more than a decade since anti-PD-1 and anti-CTLA-4 antibodies were first introduced for the treatment of unresectable melanoma. The advent of these immunotherapies has dramatically transformed the treatment landscape. In recent years, anti-PD-1 antibodies have become the cornerstone of melanoma therapy, and the development of new treatment regimens has advanced rapidly in both Eastern and Western countries. However, clinical practice has revealed lower response rates in East Asian melanoma patients compared to Caucasian populations. This discrepancy may be partially attributed to T cell immune exhaustion within the tumor microenvironment, although the detailed mechanisms remain unclear. Moreover, there is currently no established treatment for BRAF wild-type melanoma that is resistant to anti-PD-1 antibodies. This review discusses the currently available therapeutic strategies for advanced melanoma and addresses the aforementioned challenges, highlighting recent efforts in both Eastern and Western regions. Full article

(This article belongs to the Special Issue Immunotherapy for Skin Cancers)

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10 pages, 404 KiB

Open AccessArticle

Endocervical Curettage and Extended HPV Genotyping as Predictors of Residual Disease After Hysterectomy in Postmenopausal Women Previously Treated with LEEP for CIN3: A Multivariate Analysis

by Maria Teresa Bruno, Antonino Giovanni Cavallaro, Maria Fiore, Zaira Ruggeri, Martina Somma, Alessia Pagana, Giuseppe Mascellino and Antonio Simone Laganà

Cancers 2025, 17(13), 2264; https://doi.org/10.3390/cancers17132264 - 7 Jul 2025

Viewed by 346

Abstract

In postmenopausal women with high-grade cervical intraepithelial neoplasia (CIN3), hysterectomy is frequently performed after loop electrosurgical excision procedure (LEEP) due to the concern for residual disease or occult carcinoma. However, the decision to proceed with hysterectomy is often made without validated predictive criteria, [...] Read more.

In postmenopausal women with high-grade cervical intraepithelial neoplasia (CIN3), hysterectomy is frequently performed after loop electrosurgical excision procedure (LEEP) due to the concern for residual disease or occult carcinoma. However, the decision to proceed with hysterectomy is often made without validated predictive criteria, increasing the risk of overtreatment or underdiagnosis. The aim of this study is to identify independent predictors of residual CIN2+ (CIN2, CIN3, adenocarcinoma in situ, invasive carcinoma) or invasive disease in hysterectomy specimens following LEEP in this high-risk population. Methods: We conducted a multicenter retrospective study including 154 postmenopausal women (aged 50–75) who underwent total hysterectomy within 12 months after LEEP for histologically confirmed CIN3. Data collected included human papillomavirus (HPV) genotyping (pre- and post-LEEP), endocervical curettage (ECC), cone margin status, transformation zone type, and histopathological outcomes of the hysterectomy specimen. Logistic regression and ROC curve analysis were used to assess predictive factors. Results: Residual disease (CIN2+, AIS, or carcinoma) was found in 38 patients (24.7%), including 7 cases (4.5%) of occult carcinoma. Persistent high-risk HPV post-LEEP was the strongest independent predictor (adjusted OR for HPV 16/18: 74.0; p < 0.001), followed by positive ECC (OR: 3.64; p = 0.028). Cone margin status was not independently associated. The multivariate model showed good discriminative performance (AUC = 0.860; sensitivity 67.2%, specificity 72.8%). Conclusions: Our findings suggest that persistent high-risk HPV infection and positive ECC are reliable predictors of residual or occult disease. These markers should be integrated into post-LEEP follow-up protocols to better identify candidates for hysterectomy and minimize unnecessary surgeries. Full article

(This article belongs to the Section Cancer Therapy)

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15 pages, 1833 KiB

Open AccessArticle

Comparative Analysis of Gut Microbiota Responses to New SN-38 Derivatives, Irinotecan, and FOLFOX in Mice Bearing Colorectal Cancer Patient-Derived Xenografts

by Katarzyna Unrug-Bielawska, Zuzanna Sandowska-Markiewicz, Magdalena Piątkowska, Paweł Czarnowski, Krzysztof Goryca, Natalia Zeber-Lubecka, Michalina Dąbrowska, Ewelina Kaniuga, Magdalena Cybulska-Lubak, Aneta Bałabas, Małgorzata Statkiewicz, Izabela Rumieńczyk, Kazimiera Pyśniak, Michał Mikula and Jerzy Ostrowski

Cancers 2025, 17(13), 2263; https://doi.org/10.3390/cancers17132263 - 7 Jul 2025

Viewed by 374

Abstract

Background: Symbiotic gut microbiota can enhance cancer therapy efficacy, while treatment-induced dysbiosis may reduce effectiveness or increase toxicity. Our preclinical study compared the anticancer effects and impact on fecal microbiota and metabolites of two water-soluble SN-38 derivatives (BN-MePPR and BN-MOA), with those observed [...] Read more.

Background: Symbiotic gut microbiota can enhance cancer therapy efficacy, while treatment-induced dysbiosis may reduce effectiveness or increase toxicity. Our preclinical study compared the anticancer effects and impact on fecal microbiota and metabolites of two water-soluble SN-38 derivatives (BN-MePPR and BN-MOA), with those observed after treatment with Irinotecan, and the FOLFOX regimen in NOD scid gamma mice bearing patient-derived colon adenocarcinoma xenografts (CRC PDX). Methods: Five individual experiments with Irinotecan and its derivatives and eight individual experiments with FOLFOX were conducted using eight CRC PDX models. Chemotherapeutics were administered intraperitoneally 4–5 times at 5-day intervals. Fecal samples were collected before and after treatment. Microbiota composition was analyzed by 16S rRNA gene (V3–V4 regions) sequencing. Mass spectrometry was used to quantify short-chain fatty acids (SCFAs) and amino acids (AAs). Results: All treatments significantly inhibited tumor growth versus controls. However, no significant changes were observed in gut microbiota α- and β-diversity between treated and untreated groups. Tumor progression in controls was associated with increased abundance of Marvinbryantia, Lactobacillus, Ruminococcus, and [Eubacterium] nodatum group. FOLFOX-treated mice showed increased Marvinbryantia, Bacteroides, and Candidatus Arthromitus, and decreased Akkermansia. No distinct taxa changes were found in the Irinotecan or derivative groups. SCFA levels remained unchanged across groups, while BN-MePPR, BN-MOA, and Irinotecan all increased AA concentrations. Conclusions: Contrary to earlier toxicological data, these findings indicate a relatively limited impact of the tested chemotherapeutics on the gut microbiome and metabolome, emphasizing the importance of research method selection in preclinical studies. Full article

(This article belongs to the Section Cancer Therapy)

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12 pages, 943 KiB

Open AccessArticle

Sex-Specific Associations of Glycemic Status and Smoking with Bladder Cancer Risk: A Nationwide Cohort Study

by Joo-Hyun Park, Jung Yong Hong, Kyungdo Han and Jay J. Shen

Cancers 2025, 17(13), 2262; https://doi.org/10.3390/cancers17132262 - 7 Jul 2025

Viewed by 396

Abstract

Background: Sex differences in the effects of hyperglycemia and smoking on bladder cancer risk remain poorly understood, despite their known roles as modifiable risk factors. We investigated the sex-specific associations of prediabetes, diabetes, and smoking with bladder cancer risk. Methods: We [...] Read more.

Background: Sex differences in the effects of hyperglycemia and smoking on bladder cancer risk remain poorly understood, despite their known roles as modifiable risk factors. We investigated the sex-specific associations of prediabetes, diabetes, and smoking with bladder cancer risk. Methods: We analyzed data from 9,492,331 cancer-free adults (54.8% men) who underwent the 2009 Korean national health screening. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for bladder cancer incidence were calculated using Cox proportional hazards models. Results: Over a median follow-up of 8.3 years, 12,095 men and 2467 women were diagnosed with bladder cancer. The male-to-female incidence ratio was 4.1:1 among never-smokers with normoglycemia and 2.7:1 among ever-smokers with diabetes. In women, both prediabetes and diabetes were associated with elevated bladder cancer risk (aHRs, 95% CIs: 1.12, 1.02–1.24; and 1.27, 1.13–1.43). In men, only diabetes showed an increased risk (aHR: 1.22, 1.12–1.32). Combined diabetes and smoking increased the risk synergistically in women (aHR: 2.75, 1.95–3.87; synergy index = 2.38, p < 0.01), while the effect was additive in men (aHR: 1.82, 1.70–1.95). Conclusions: The typical male predominance in bladder cancer incidence appeared attenuated in the presence of hyperglycemia and smoking, suggesting that these risk factors may have a relatively greater impact on bladder cancer risk among women. These findings underscore the importance of targeted bladder cancer prevention strategies, with particular attention to women with hyperglycemia who smoke, given their disproportionately elevated risk. Full article

(This article belongs to the Section Cancer Epidemiology and Prevention)

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21 pages, 18499 KiB

Open AccessArticle

Impact of a Surgical Approach on Endometrial Cancer Survival According to ESMO/ESGO Risk Classification: A Retrospective Multicenter Study in the Northern Italian Region

by Vincenzo Dario Mandato, Anna Myriam Perrone, Debora Pirillo, Gino Ciarlini, Gianluca Annunziata, Alessandro Arena, Carlo Alboni, Ilaria Di Monte, Vito Andrea Capozzi, Andrea Amadori, Ruby Martinello, Federica Rosati, Marco Stefanetti, Andrea Palicelli, Giacomo Santandrea, Renato Seracchioli, Roberto Berretta, Lorenzo Aguzzoli, Federica Torricelli and Pierandrea De Iaco

Cancers 2025, 17(13), 2261; https://doi.org/10.3390/cancers17132261 - 7 Jul 2025

Viewed by 351

Abstract

Background: Following the results of the Laparoscopic Approach to Carcinoma of the Cervix (LACC) trial, doubts have arisen about the safety of laparoscopy in the treatment of endometrial cancer. Methods: A retrospective multicenter cohort study which included all endometrial cancer (EC) patients [...] Read more.

Background: Following the results of the Laparoscopic Approach to Carcinoma of the Cervix (LACC) trial, doubts have arisen about the safety of laparoscopy in the treatment of endometrial cancer. Methods: A retrospective multicenter cohort study which included all endometrial cancer (EC) patients who underwent a hysterectomy in Emilia Romagna hospitals from 2000 to 2019. All cases were revised and classified according to the 2009 International Federation of Gynaecology and Obstetrics (FIGO) staging system. The different impacts of the surgical approach on survival were stratified according to the recurrence risk from the 2016 European Society for Medical Oncology (ESMO)–European Society of Gynaecological Oncology (ESGO) classification system. The clinical characteristics and oncological outcome of patients treated by laparoscopy were compared with those treated by laparotomy. Results: A total of 2402 EC patients were included in the study. The use of laparoscopy has increased over the years, reaching 81% of procedures in 2019. Laparoscopy reduced complications and hospital stay. Laparoscopy was preferred to treat low, intermediate, and intermediate/high-risk patients. Laparoscopy showed no adverse effects on overall survival (OS) in any recurrence risk class. Particularly in high-risk EC patients, laparoscopy was associated with an increased OS in comparison with women treated by laparotomy regardless of the use of adjuvant therapy. Conclusions: Laparoscopy should always be chosen to treat EC of any risk class. The goal is to ensure correct treatment and oncological safety regardless of the surgical approach. Full article

(This article belongs to the Special Issue Lymph Node Dissection for Gynecologic Cancers)

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16 pages, 2092 KiB

Open AccessArticle

Augmented Reality-Assisted Placement of Surgical Guides and Osteotomy Execution for Pelvic Tumour Resections: A Pre-Clinical Feasibility Study Using 3D-Printed Models

by Tanya Fernández-Fernández, Javier Orozco-Martínez, Amaia Iribar-Zabala, Elena Aguilera Jiménez, Carla de Gregorio-Bermejo, Lydia Mediavilla-Santos, Javier Pascau, Mónica García-Sevilla, Rubén Pérez-Mañanes and Jose Antonio Calvo-Haro

Cancers 2025, 17(13), 2260; https://doi.org/10.3390/cancers17132260 - 7 Jul 2025

Viewed by 288

Abstract

Objectives: This pre-clinical feasibility study evaluates the accuracy of a novel augmented reality-based (AR-based) guidance technology using head-mounted displays (HMDs) for the placement of patient-specific instruments (PSIs)—also referred to as surgical guides—and osteotomy performance in pelvic tumour resections. The goal is to [...] Read more.

Objectives: This pre-clinical feasibility study evaluates the accuracy of a novel augmented reality-based (AR-based) guidance technology using head-mounted displays (HMDs) for the placement of patient-specific instruments (PSIs)—also referred to as surgical guides—and osteotomy performance in pelvic tumour resections. The goal is to improve PSI placement accuracy and osteotomy execution while assessing user perception and workflow efficiency. Methods: The study was conducted on ten 3D-printed pelvic phantoms derived from CT scans of cadaveric specimens. Custom PSIs were designed and printed to guide osteotomies at the supraacetabular, symphysial, and ischial regions. An AR application was developed for the HoloLens 2 HMD to display PSI location and cutting planes. The workflow included manual supraacetabular PSI placement, AR-guided placement of the other PSIs and osteotomy execution. Postoperative CT scans were analysed to measure angular and distance errors in PSI placement and osteotomies. Task times and user feedback were also recorded. Results: The mean angular deviation for PSI placement was 2.20°, with a mean distance error of 1.19 mm (95% CI: 0.86 to 1.52 mm). Osteotomies showed an overall mean angular deviation of 3.73° compared to planned cuts, all within the predefined threshold of less than 5°. AR-assisted guidance added less than two minutes per procedure. User feedback highlighted the intuitive interface and high usability, especially for visualising cutting planes. Conclusions: Integrating AR through HMDs is a feasible and accurate method for enhancing PSI placement and osteotomy performance in pelvic tumour resections. The system provides reliable guidance even in cases of PSI failure and adds minimal time to the surgical workflow while significantly improving accuracy. Further validation in cadaveric models is needed to ensure its clinical applicability. Full article

(This article belongs to the Special Issue Clinical Treatment of Osteosarcoma)

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16 pages, 603 KiB

Open AccessReview

Current Updates on Surgical Management of Patients with Early-Stage Cervical Cancer

by María Clara Santía, Tommaso Meschini, Heng-Cheng Hsu, Paula Mateo-Kubach, Elise M. Yates, Karolina Kilowski, Behrouz Zand, Rene Pareja and Pedro T. Ramirez

Cancers 2025, 17(13), 2259; https://doi.org/10.3390/cancers17132259 - 7 Jul 2025

Viewed by 519

Abstract

The recommended treatment for early-stage cervical cancer (FIGO 2018 stages IA–IB2 and selected IIA1) is surgery, followed by either observation or adjuvant therapy, based on individual risk factors. Surgical management has evolved from extensive radical procedures to more conservative strategies, allowing for fertility-preserving [...] Read more.

The recommended treatment for early-stage cervical cancer (FIGO 2018 stages IA–IB2 and selected IIA1) is surgery, followed by either observation or adjuvant therapy, based on individual risk factors. Surgical management has evolved from extensive radical procedures to more conservative strategies, allowing for fertility-preserving options in appropriately selected patients. In 2018, a landmark study (LACC trial) evaluated the surgical approach to radical hysterectomy, comparing open vs. minimally invasive surgery. The results demonstrated that minimally invasive surgery was associated with worse disease-free and overall survival, leading to guidelines changes that recommend the open radical hysterectomy as the new standard of care. More recently, results from the prospective randomized SHAPE trial demonstrated that in well-selected patients with low-risk early-stage cervical cancer, recurrence rates are comparable between simple hysterectomy and radical hysterectomy. An ongoing study, the CONTESSA trial, is evaluating the role of neoadjuvant chemotherapy in the setting of fertility preservation for lesions measuring 2–4 cm. In addition, ongoing studies are evaluating different surgical approaches for both simple hysterectomy (LASH trial) and radical hysterectomy (ROCC/GOG-3043 and RACC trials), with a focus on comparing oncologic outcomes. Attention has also turned to refining lymph node assessment. Sentinel lymph node biopsy has become a standard staging strategy with reduced morbidity. The SENTICOL I-II and SENTIX/ENGOT-Cx2 trials support its safety and diagnostic accuracy in early-stage disease. This article offers a comprehensive overview of recently published prospective trials that have shaped clinical practice in the management of early-stage cervical cancer. It focuses on surgical approaches and radicality, the role of sentinel lymph node mapping, and fertility-sparing treatments. The review further draws attention to ongoing investigations and novel studies that may influence future directions in the field. Full article

(This article belongs to the Special Issue Surgery for Cervical Cancer)

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11 pages, 209 KiB

Open AccessReview

Treatment Intensification Prior to Radical Prostatectomy for Clinically Localized Prostate Cancer

by Carlos Jesus Perez Kerkvliet, Joon Yau Leong, Rasheed A. M. Thompson, Kevin Kayvan Zarrabi, William Kevin Kelly, Costas Lallas, Leonard Gomella and Mihir Shah

Cancers 2025, 17(13), 2258; https://doi.org/10.3390/cancers17132258 - 7 Jul 2025

Viewed by 377

Abstract

Current guidelines recommend either radical prostatectomy (RP) or radiation with androgen deprivation therapy (ADT) for unfavorable intermediate- or high-risk prostate cancer. There has been emerging interest in the potential benefits of neoadjuvant ADT prior to RP for this population. Past trials indicate neoadjuvant [...] Read more.

Current guidelines recommend either radical prostatectomy (RP) or radiation with androgen deprivation therapy (ADT) for unfavorable intermediate- or high-risk prostate cancer. There has been emerging interest in the potential benefits of neoadjuvant ADT prior to RP for this population. Past trials indicate neoadjuvant ADT may be associated with reduced surgical complexity, pathologic downstaging, decreased positive margins, and decreased rates of nodal positivity, although they have not shown benefits for cancer progression and survival. Accordingly, neoadjuvant ADT is currently not recommended for surgical patients. Conversely, ADT is a mainstay of treatment in metastatic disease, and interest remains in expanding its use towards patients with clinically localized disease. There are several ongoing trials of second-generation androgen blockers such as enzalutamide, darolutamide, radiopharmaceuticals, and poly (ADP-ribose) polymerase (PARP) inhibitors to explore long-term cancer-specific survival benefits with neoadjuvant use. In this narrative review, we provide a comprehensive overview of the recent literature and ongoing efforts to incorporate neoadjuvant therapy for clinically localized prostate cancer patients who are at high-risk of recurrence after prostatectomy. Full article

(This article belongs to the Section Cancer Therapy)

17 pages, 1445 KiB

Open AccessArticle

A Deep Learning Model Integrating Clinical and MRI Features Improves Risk Stratification and Reduces Unnecessary Biopsies in Men with Suspected Prostate Cancer

by Emiliano Bacchetti, Axel De Nardin, Gianluca Giannarini, Lorenzo Cereser, Chiara Zuiani, Alessandro Crestani, Rossano Girometti and Gian Luca Foresti

Cancers 2025, 17(13), 2257; https://doi.org/10.3390/cancers17132257 - 7 Jul 2025

Viewed by 332

Abstract

Background: Accurate upfront risk stratification in suspected clinically significant prostate cancer (csPCa) may reduce unnecessary prostate biopsies. Integrating clinical and Magnetic Resonance Imaging (MRI) variables using deep learning could improve prediction. Methods: We retrospectively analysed 538 men who underwent MRI and biopsy between [...] Read more.

Background: Accurate upfront risk stratification in suspected clinically significant prostate cancer (csPCa) may reduce unnecessary prostate biopsies. Integrating clinical and Magnetic Resonance Imaging (MRI) variables using deep learning could improve prediction. Methods: We retrospectively analysed 538 men who underwent MRI and biopsy between April 2019-September 2024. A fully connected neural network was trained using 5-fold cross-validation. Model 1 included clinical features (age, prostate-specific antigen [PSA], PSA density, digital rectal examination, family history, prior negative biopsy, and ongoing therapy). Model 2 used MRI-derived Prostate Imaging Reporting and Data System (PI-RADS) categories. Model 3 used all previous variables as well as lesion size, location, and prostate volume as determined on MRI. Results: Model 3 achieved the highest area under the receiver operating characteristic curve (AUC = 0.822), followed by Model 2 (AUC = 0.778) and Model 1 (AUC = 0.716). Sensitivities for detecting clinically significant prostate cancer (csPCa) were 87.4%, 91.6%, and 86.8% for Models 1, 2, and 3, respectively. Although Model 3 had slightly lower sensitivity than Model 2, it showed higher specificity, reducing false positives and avoiding 43.4% and 21.2% more biopsies compared to Models 1 and 2. Decision curve analysis showed M2 had the highest net benefit at risk thresholds ≤ 20%, while M3 was superior above 20%. Conclusions: Model 3 improved csPCa risk stratification, particularly in biopsy-averse settings, while Model 2 was more effective in cancer-averse scenarios. These models support personalized, context-sensitive biopsy decisions. Full article

(This article belongs to the Special Issue Radiomics in Cancer)

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25 pages, 1380 KiB

Open AccessReview

Redefining the Fight Against SCLC: Standards, Innovations, and New Horizons

by Marcel Kemper, Lea Elisabeth Reitnauer, Georg Lenz, Georg Evers and Annalen Bleckmann

Cancers 2025, 17(13), 2256; https://doi.org/10.3390/cancers17132256 - 7 Jul 2025

Viewed by 570

Abstract

Background: Small cell lung cancer (SCLC) remains a highly aggressive malignancy with a poor prognosis. Despite multimodal standard therapies, most patients relapse within months, and second-line treatment options such as topotecan offer only limited benefit. Novel therapeutic strategies are therefore urgently needed. Methods: [...] Read more.

Background: Small cell lung cancer (SCLC) remains a highly aggressive malignancy with a poor prognosis. Despite multimodal standard therapies, most patients relapse within months, and second-line treatment options such as topotecan offer only limited benefit. Novel therapeutic strategies are therefore urgently needed. Methods: This narrative review is based on a selective literature search conducted via PubMed and ClinicalTrials.gov (last updated June 2025). Results: Emerging treatment strategies include bispecific T-cell engagers (e.g., tarlatamab), antibody-drug conjugates (ADCs) such as sacituzumab govitecan, DS-7300, and ZL-1310, as well as targeted therapies. Among these, tarlatamab has demonstrated improved survival outcomes with an acceptable safety profile and is poised to become the new second-line standard. In contrast, ADCs and targeted agents have shown only modest efficacy and have yet to deliver meaningful survival benefits, often accompanied by increased toxicity. Additionally, the identification of molecular subtypes of SCLC has revealed subtype-specific differences in treatment response. However, clinical translation is challenged by intratumoral heterogeneity, plasticity, and the lack of standardized diagnostic assays. Conclusions: While tarlatamab represents a major therapeutic advancement, other agents remain in early clinical development and require validation in large, randomized trials. The clinical implementation of molecular subtyping remains limited, though it holds promise for future personalized treatment approaches. Despite recent progress, SCLC continues to pose substantial therapeutic challenges, emphasizing the need for improved treatment strategies and validated predictive biomarkers. Full article

(This article belongs to the Special Issue Advances in Targeted Therapies in Cancer (2nd Edition))

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22 pages, 3032 KiB

Open AccessArticle

MYC Regulates a DNA Repair Gene Expression Program in Small Cell Carcinoma of the Ovary, Hypercalcemic Type

by James R. Evans, Jing Wang, Cinthia N. Reed, Joy H. Creighton, Kaylee B. Garrison, Abigail N. Robertson, Ashley Lira-Rivera, Diondre’ D. Baisden, William P. Tansey, Rafet Al-Tobasei, Jessica D. Lang, Qi Liu and April M. Weissmiller

Cancers 2025, 17(13), 2255; https://doi.org/10.3390/cancers17132255 - 7 Jul 2025

Viewed by 417

Abstract

Background/Objectives: SCCOHT is an aggressive and often fatal cancer that belongs to the ~20% of cancers defined by mutations to subunits of the SWI/SNF chromatin remodeling complex. In SCCOHT, mutations to the SMARCA4 gene, which encodes the SWI/SNF ATPase BRG1, are sufficient to [...] Read more.

Background/Objectives: SCCOHT is an aggressive and often fatal cancer that belongs to the ~20% of cancers defined by mutations to subunits of the SWI/SNF chromatin remodeling complex. In SCCOHT, mutations to the SMARCA4 gene, which encodes the SWI/SNF ATPase BRG1, are sufficient to impair SWI/SNF function. This single genetic lesion leads to a cascade of events that promote tumorigenesis, some of which may involve the intersection of SWI/SNF with oncogenic pathways such as those regulated by the MYC oncogene. In SCCOHT tumors and other cancers marked by SWI/SNF subunit mutation, MYC target genes are recurrently activated, pointing to a relationship between SWI/SNF and MYC that has yet to be fully explored. Methods: In this study, we investigate the contribution of MYC to SCCOHT biology by performing a combination of chromatin binding and transcriptome assays in genetically engineered SCCOHT cell lines, with subsequent validation using patient tumor expression data. Results: We find that MYC binds to thousands of active promoters in the BIN-67 SCCOHT cell line and that the depletion of MYC results in a broad range of gene expression changes with a notable effect on the expression of genes related to DNA repair. We uncover an MYC-regulated DNA repair gene expression program in BIN-67 cells that is antagonized by BRG1 reintroduction. Finally, we identify a DNA repair gene signature that is upregulated in SCCOHT tumors and in tumors defined by loss of the SWI/SNF subunit SNF5. Conclusions: Collectively, these data implicate MYC as a robust regulator of DNA repair gene expression in SCCOHT and lay a foundation for future studies focused on interrogating the relationship between BRG1 and MYC. Full article

(This article belongs to the Special Issue Chromatin-Remodeling Factors in Cancer Cells)

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15 pages, 1656 KiB

Open AccessArticle

Transarterial Chemoembolization Outperforms Radioembolization in Early- and Intermediate-Stage Hepatocellular Carcinoma: A Multicenter Retrospective Study

by Faisal M. Sanai, Adnan Alzanbagi, Mohammed Arabi, Sarah S. Alfawaz, Khalid I. Bzeizi, Mohammed Almatrafi, Abdulmalik M. Alsabban, Jameel Bardesi, Hamdan S. Alghamdi, Mohamed Shawkat, Talal M. Alotaibi, Khairat H. Alameer, Shadi Saleem, Saad Abualganam, Abdulaziz M. Tashkandi, Noha H. Guzaiz, Nesreen H. Abourokbah, Hassan O. Alfakieh, Majed Almaghrabi, Abeer A. Alabdullah, Lujain H. Aljohani, Nuwayyir A. Alqasimi, Saad Aldosari, Azzam Khankan, Dieter Broering and Saleh A. Alqahtani Show full author list Hide full author list

Cancers 2025, 17(13), 2254; https://doi.org/10.3390/cancers17132254 - 7 Jul 2025

Viewed by 453

Abstract

Background: Transarterial radioembolization (TARE) with Yttrium-90 microspheres is an established therapy for unresectable hepatocellular carcinoma (HCC). However, its clinical efficacy compared to transarterial chemoembolization (TACE) remains unclear. Methods: We retrospectively reviewed 279 consecutive patients undergoing TARE (n = 104) or TACE (n = [...] Read more.

Background: Transarterial radioembolization (TARE) with Yttrium-90 microspheres is an established therapy for unresectable hepatocellular carcinoma (HCC). However, its clinical efficacy compared to transarterial chemoembolization (TACE) remains unclear. Methods: We retrospectively reviewed 279 consecutive patients undergoing TARE (n = 104) or TACE (n = 175) at four tertiary centers. Patients with metastatic disease, locally advanced HCC, or Child–Pugh (CP) C were excluded. Data on treatment, adverse events, survival outcomes (median overall survival [mOS], and objective response rates [by modified Response Evaluation Criteria in Solid Tumors; mRECIST]) were collected. Results: The median follow-up of the cohort was 27 months (IQR 13–50), the mean age was 67.6 ± 10.1 years, and 207 (74.2%) were male. The cohort was balanced in age, performance status, CP class, and HCC etiology. Maximum tumor diameter was significantly larger in the TARE cohort compared to the TACE cohort (4.4 vs. 3.1 cm, p < 0.001), including within the BCLC 0/A (4.2 vs. 2.7 cm, p = 0.001) and BCLC B (5.0 vs. 4.0 cm, p = 0.049) subgroups. The mOS was longer with TACE (37 vs. 22 months; hazard ratio [HR] 1.65, 95% CI: 1.19–2.29, p = 0.002). In BCLC 0/A patients, TACE yielded longer mOS (60 vs. 25 months; HR 2.35, 95% CI: 1.17–4.69; p = 0.016). In BCLC B, mOS was longer with TACE (32 vs. 20 months), but was not statistically significant (HR 1.39, 95% CI: 0.96–2.03, p = 0.080). In BCLC 0/A, complete response rates were higher with TACE (43.2% vs. 34.3%, p = 0.012). Hepatic decompensation was more frequent with TARE- (26.0%) than with TACE-treated patients (13.7%, p = 0.010). Conclusions: TACE demonstrated superior survival outcomes over TARE, particularly in early-stage disease. These results advocate for a more nuanced selection of embolization therapies in these patients. Full article

(This article belongs to the Section Cancer Therapy)

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41 pages, 5261 KiB

Open AccessReview

Merkel Cell Carcinoma: An Updated Review Focused on Bone and Bone Marrow Metastases

by Biagio Scotti, Elisabetta Broseghini, Costantino Ricci, Barbara Corti, Costanza Viola, Cosimo Misciali, Carlotta Baraldi, Sabina Vaccari, Martina Lambertini, Federico Venturi, Elisabetta Magnaterra, Aurora Alessandrini, Tiziano Ferrari, Massimo Lepri, Gabriele Argenziano, Barbara Melotti, Elena Campione, Davide Campana, Manuela Ferracin and Emi Dika

Cancers 2025, 17(13), 2253; https://doi.org/10.3390/cancers17132253 - 6 Jul 2025

Viewed by 661

Abstract

Background/objectives: Despite advancements in early diagnosis and clinical practices guided by standardized care protocols, Merkel cell carcinoma (MCC) is marked by an unfavorable prognosis with a 5-year relative survival rate of 65%, based primarily on data collected prior to the introduction of immunotherapy. [...] Read more.

Background/objectives: Despite advancements in early diagnosis and clinical practices guided by standardized care protocols, Merkel cell carcinoma (MCC) is marked by an unfavorable prognosis with a 5-year relative survival rate of 65%, based primarily on data collected prior to the introduction of immunotherapy. Regional nodal metastases affect 40–50% of MCC patients, while approximately 33% experience distant dissemination. Among these, bone and bone marrow metastases are particularly notable, although the characteristics and clinical implications of this metastatic disease in MCC remain poorly understood. Methods: A comprehensive review was conducted using the Medline database (via PubMed) up to January 2025. The search strategy included the string “(Merkel cell carcinoma AND (bone OR marrow))”. Results: A total of 1133 (69.3% male and 30.7% female) patients diagnosed with advanced MCC were collected. The median (IQR) age at diagnosis was 67.5 (12.65) years old. Overall, 201 (20.8%) cases of bone and/or bone marrow metastases were identified and linked to a primary known MCC in 75.7% of cases. Bone metastases (BMs) appear as the third most common metastatic site, following the liver (second) and lymph nodes (first). They show mixed biological and radiological behavior, with a marked preference for the axial skeleton over the appendicular one. Addressing the characteristics of metastatic bone disease, neurological symptoms were the most documented, whereas bone marrow involvement and leukemic spread seemed to be primarily related to immunosuppression. Multimodal treatment strategies, including platinum-based chemotherapy and radiotherapy, were the primary approaches adopted, reflecting therapeutic practices from the pre-immunotherapy era. Conclusions: The pattern of metastatic spread in MCC differs among studies, with the bones resulting as the third most common site of distant spread. Excluding head and neck MCC, which seems to be more regularly associated with liver metastases, the relationship between the primary tumor site and the development of bone or bone marrow metastases appears inconsistent. Overall, BMs mostly correlated with advanced MCC stages and poorer survival outcomes, with a median overall survival (OS) of 8 months (range 12.75–4). The integration of international guidelines, evolving evidence from clinical trials, and the expanding role of immune checkpoint inhibitors (ICIs) will contribute to improving systemic disease control and enhance patient care. Full article

(This article belongs to the Special Issue Exploring Skin Cancer: Insights into New Diagnostic, Prognostic, and Therapeutic Strategies)

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14 pages, 1180 KiB

Open AccessArticle

Clinical and Pathological Features and Survival Outcomes of Breast Cancers with Intermediate ER Expression

by Jonathan Hammond, Nicholas Lambert and Ioannis A. Voutsadakis

Cancers 2025, 17(13), 2252; https://doi.org/10.3390/cancers17132252 - 5 Jul 2025

Viewed by 339

Abstract

Background: Breast cancer is the most prevalent women’s cancer, representing about a third of all cancers diagnosed in women. Estrogen receptor (ER) is an important transcription factor expressed in 70% to 75% of all breast cancers. Of these breast cancers, the majority express [...] Read more.

Background: Breast cancer is the most prevalent women’s cancer, representing about a third of all cancers diagnosed in women. Estrogen receptor (ER) is an important transcription factor expressed in 70% to 75% of all breast cancers. Of these breast cancers, the majority express ER robustly in 91–100% of tumor cells. However, a minority of breast cancers express ER in intermediate levels between 11% and 90% of tumor cells. The characteristics and outcomes of this intermediate subset of ER-positive breast cancers are not well studied. Methods: We retrospectively reviewed the medical records of all breast cancer patients treated in our Cancer Center over a period of 8 years. Patients were grouped according to the level of ER expression in tumors with negative/low ER expression, intermediate ER expression, and high ER expression, and the groups were compared for tumor characteristics and outcomes. Results: Patients with high ER levels (91% to 100%) represented 75.6% (600 of 794 patients), patients with intermediate ER expression represented 11.5% of the entire group (91 of 794 patients), and patients with negative/low ER expression (ER expression 0–10%) represented 12.9% of the entire cohort (103 of 794 patients). Patients with intermediate ER expression presented at a younger age than patients with high-ER cancers, as well as a more advanced stage and higher grade. These characteristics were more akin to patients with negative/low ER levels. Mastectomy was the surgical method of resection more commonly in ER-intermediate tumors than in ER-high tumors. The relapse-free survival (RFS) of patients with ER-intermediate cancers was worse than the RFS of patients that expressed ER robustly. Conclusion: The level of expression of ER defines groups of patients with varying characteristics and prognoses. Patients in the intermediate ER expression group had notable differences from patients in the high ER expression group including younger age, (more often) a higher grade, and low PR positivity. Differences observed between the group of patients with intermediate ER expression and that with high ER expression may help to prioritize therapeutic algorithms. Full article

(This article belongs to the Special Issue Advances in Invasive Breast Cancer: Treatment and Prognosis (2nd Edition))

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15 pages, 758 KiB

Open AccessReview

Myeloid-Derived Suppressor Cells (MDSCs) at the Crossroad of Senescence and Cancer

by Giovanna Talarico, Stefania Orecchioni, Paolo Falvo and Francesco Bertolini

Cancers 2025, 17(13), 2251; https://doi.org/10.3390/cancers17132251 - 4 Jul 2025

Viewed by 358

Abstract

The family of myeloid-derived suppressor cells (MDSCs) includes a heterogeneous group of partially immature cells belonging to the myeloid lineage with potent immunosuppressive functions. They might be increased in the peripheral blood of cancer patients and in the microenvironment of cancer lesions, where [...] Read more.

The family of myeloid-derived suppressor cells (MDSCs) includes a heterogeneous group of partially immature cells belonging to the myeloid lineage with potent immunosuppressive functions. They might be increased in the peripheral blood of cancer patients and in the microenvironment of cancer lesions, where they act in suppressing adaptive and innate immune cells, promoting tumor progression, and facilitating resistance to therapy. Several—albeit still limited—studies have shown higher levels of MDSCs in elderly cancer patients, correlating with poorer outcomes and a reduced response to immunotherapies. Thus, MDSCs may serve as biomarkers for prognosis or therapy response in this population, and MDSC-targeting therapies aimed at reducing their number or function may enhance the effectiveness of immunotherapies in older adults. Additionally, a better understanding of MDSCs may help to overcome some age-related barriers in cancer treatments. Full article

(This article belongs to the Special Issue New Insights in the Role of Myeloid-Derived Suppressor Cells (MDSCs) in Cancer)

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13 pages, 1141 KiB

Open AccessArticle

Multi-Cancer Genome Profiling for Neurotrophic Tropomyosin Receptor Kinase (NTRK) Fusion Genes: Analysis of Profiling Database of 88,688 Tumors

by Hinano Nishikubo, Kyoka Kawabata, Saki Kanei, Rika Aoyama, Dongheng Ma, Tomoya Sano, Daiki Imanishi, Takashi Sakuma, Koji Maruo, Canfeng Fan, Yurie Yamamoto and Masakazu Yashiro

Cancers 2025, 17(13), 2250; https://doi.org/10.3390/cancers17132250 - 4 Jul 2025

Viewed by 280

Abstract

Background/Objectives: The neurotrophic tropomyosin receptor kinase (NTRK) genes NTRK1, NTRK2, and NTRK3 encode tyrosine kinase receptors, and their fusion genes are known as the oncogenic driver genes for cancer. This study aimed to compare the diagnostic ability of NTRK fusion [...] Read more.

Background/Objectives: The neurotrophic tropomyosin receptor kinase (NTRK) genes NTRK1, NTRK2, and NTRK3 encode tyrosine kinase receptors, and their fusion genes are known as the oncogenic driver genes for cancer. This study aimed to compare the diagnostic ability of NTRK fusion among five types of multi-cancer genome profiling tests (multi-CGP tests) and determine a useful multi-CGP test for NTRK fusion, recorded in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan. This study aimed to compare the diagnostic results for NTRK fusions among the five different CGP tests. Methods: A total of 88,688 tumor cases were enrolled in the C-CAT profiling database from 2019 to 2024. The detection frequency of NTRK fusion genes was compared to the results for five multi-CGP tests: NCC Oncopanel, FoundationOne CDx (F1), FoundationOne Liquid (F1L), GenMineTOP (GMT), and Guardant360. Results: NTRK fusion genes were detected in 175 (0.20%) of the 88,688 total cases. GMT, which is equipped with RNA sequencing function, frequently detected NTRK fusion genes (20 of 2926 cases; 0.68%) in comparison with the other four multi-CGP tests that do not have RNA sequencing analysis. GMT showed significantly (p < 0.05) higher diagnostic ability for NTRK fusions compared with the other four multi-CGP tests. Especially, NTRK2 fusion was significantly (p < 0.001) more highly determined by GMT than it was by the other four multi-CGP tests. The detection rates for FGFR1 and FGFR3 were significantly higher in GMT than in other multi-CGP tests. In contrast, the detection rates of the ALK and RET fusion genes were significantly higher in F1L. Conclusions: GMT, which is equipped with RNA sequencing analysis, might show a useful diagnostic ability for NTRK fusions, especially for NTRK2 fusion genes. Full article

(This article belongs to the Special Issue Cell-Free DNA as Prognostic and Predictive Biomarker in Solid Cancers (2nd Edition))

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17 pages, 1787 KiB

Open AccessArticle

Tumor Segmentation on PSMA PET/CT Predicts Survival in Biochemical Recurrence of Prostate Cancer: A Retrospective Study Using [⁶⁸Ga]Ga-PSMA-11 and [¹⁸F]-PSMA-1007

by Ken Kudura, Yves Schaulin, Arnoud J. Templeton, Tobias Zellweger, Wolfgang Harms, Raphael Georis, Michael C. Kreissl and Robert Foerster

Cancers 2025, 17(13), 2249; https://doi.org/10.3390/cancers17132249 - 4 Jul 2025

Viewed by 464

Abstract

Background: PSMA PET/CT imaging has become a cornerstone in the management of prostate cancer, particularly in the setting of biochemical recurrence (BCR). While semi-quantitative parameters such as SUVmean have been evaluated as prognostic biomarkers in metastatic castration-resistant prostate cancer (mCRPC), particularly after [...] Read more.

Background: PSMA PET/CT imaging has become a cornerstone in the management of prostate cancer, particularly in the setting of biochemical recurrence (BCR). While semi-quantitative parameters such as SUVmean have been evaluated as prognostic biomarkers in metastatic castration-resistant prostate cancer (mCRPC), particularly after the VISION trial, the prognostic role of volumetric measures such as Total Molecular Volume (TMV) remain largely unexplored, especially in earlier stages of the disease such as in biochemical recurrence following primary treatment. Methods: This retrospective monocentric study included 84 patients with BCR who underwent PSMA PET/CT imaging between 2020 and 2021 using either [⁶⁸Ga]Ga-PSMA-11(Ga-PSMA) or [¹⁸F]-PSMA-1007 (F-PSMA) as tracers. Total tumor burden was assessed through manual 3D segmentation to derive whole-body Total Molecular Volume (wb TMV) and Total Lesion PSMA (wb TL-PSMA). Clinical and imaging variables were correlated with overall survival (OS) and progression-free survival (PFS) using Cox regression models. Kaplan–Meier analyses were performed based on wb TMV and thresholds determined by the Youden index. Results: A PSMA PET/CT correlation for BCR was identified in 69% of patients, with comparable detection rates between tracers (Ga-PSMA 67% vs. F-PSMA 63%, p = 0.7). A higher wb TMV was significantly associated with worse OS (HR 2.20, p < 0.001) and PFS (HR 2.01, p < 0.001) in univariable analyses. In multivariable models, log₂(wb TMV) remained an independent prognostic factor for PFS (HR 1.78, p = 0.005). Patients with log₂(wb TMV) > 2.87 exhibited significantly poorer survival outcomes. A PSA at diagnosis > 17 ng/mL also predicted shorter PFS. Conclusions: Tumor segmentation from PSMA PET/CT imaging provides powerful prognostic information in patients with biochemical recurrence of prostate cancer, independently of the tracer used. The wb TMV represents a promising volumetric biomarker for future risk stratification and therapeutic decision-making, particularly in earlier stages of prostate cancer progression, where predictive imaging biomarkers remain largely undefined. Full article

(This article belongs to the Special Issue Advancements in the Diagnosis and Surgical Treatment of Prostate Cancer)

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18 pages, 1413 KiB

Open AccessArticle

Laparoscopic Microwave Ablation and Salvage Liver Transplantation in Patients with Hepatocellular Carcinoma

by Alessandro Vitale, Marco Brolese, Ilaria Govoni, Chiara Naldini, Nicola Canitano, Enrico Gringeri, Francesco D’Amico, Domenico Bassi, Francesco Enrico D’Amico, Jacopo Lanari, Alessandro Furlanetto, Virginia Padoan, Daniel Salinas and Umberto Cillo

Cancers 2025, 17(13), 2248; https://doi.org/10.3390/cancers17132248 - 4 Jul 2025

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Abstract

Background/Objectives: Salvage liver transplantation (SLT) is a well-established option for hepatocellular carcinoma (HCC) recurrence after liver resection. Laparoscopic microwave ablation (L-MWA) represents another curative strategy for early-stage HCC. However, its role within this therapeutic framework remains unexplored. Methods: Between 2014 and [...] Read more.

Background/Objectives: Salvage liver transplantation (SLT) is a well-established option for hepatocellular carcinoma (HCC) recurrence after liver resection. Laparoscopic microwave ablation (L-MWA) represents another curative strategy for early-stage HCC. However, its role within this therapeutic framework remains unexplored. Methods: Between 2014 and 2023, we treated 1341 patients with HCC using L-MWA. From this cohort, patients with Child-Pugh class A liver function, HCC within the Milan criteria, no contraindications to transplantation, and ≥12 months of follow-up were selected. SLT failure was defined as non-transplantable recurrence or death, resulting in the loss of a potentially curative therapeutic opportunity. The primary endpoint was overall survival (OS); secondary endpoints included predictors of survival and SLT failure. Results: A total of 341 patients met the inclusion criteria. Five-year OS was 62%. Independent predictors of poorer survival included the presence of cardiac disease or oesophageal varices, a Child-Pugh score of 6, tumour size, and elevated alpha-fetoprotein (AFP) levels. Treatment was successful in 255 patients (74.8%): 102 (29.9%) underwent SLT, 67 (19.6%) received alternative therapies, and 93 (27.3%) remained recurrence-free. Treatment failure occurred in 86 patients (25.2%) due to non-transplantable recurrence or death. Independent predictors of failure included older age, non-HBV aetiology, and elevated AFP levels. Five-year OS rates were 79% in the success group and 22% in the failure group (p < 0.001). Conclusions: A combined L-MWA and SLT strategy is safe and effective, yielding a 62% 5-year OS rate. This approach supports more efficient graft use with a consequent increase in the population transplant benefit. Improved selection may further reduce failure rates. Full article

(This article belongs to the Section Transplant Oncology)

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16 pages, 1541 KiB

Open AccessSystematic Review

Is [¹⁷⁷Lu]Lu-PSMA-617 Redefining Value in mCRPC Care? A Meta-Analysis of Clinical and Economic Endpoints

by Francesco Fiorica, Maria Viviana Candela, Teodoro Sava, Matteo Salgarello, Jacopo Giuliani, Singh Navdeep, Antonella Franceschetto, Daniela Grigolato, Emilia Durante, Erica Palesandro, Enrico Altiero Giusto, Consuelo Buttigliero and Marcello Tucci

Cancers 2025, 17(13), 2247; https://doi.org/10.3390/cancers17132247 - 4 Jul 2025

Viewed by 826

Abstract

Background: Radioligand therapy with [¹⁷⁷Lu]Lu-PSMA-617 represents an emerging treatment for metastatic castration-resistant prostate cancer (mCRPC). Its clinical positioning relative to standard therapies remains under discussion. Objective: To compare overall survival (OS), radiographic progression-free survival (rPFS), PSA response, and treatment burden across [...] Read more.

Background: Radioligand therapy with [¹⁷⁷Lu]Lu-PSMA-617 represents an emerging treatment for metastatic castration-resistant prostate cancer (mCRPC). Its clinical positioning relative to standard therapies remains under discussion. Objective: To compare overall survival (OS), radiographic progression-free survival (rPFS), PSA response, and treatment burden across randomised trials evaluating [¹⁷⁷Lu]Lu-PSMA-617 versus androgen receptor pathway inhibitors (ARTA), Cabazitaxel, or standard of care (SOC). Evidence Acquisition: We conducted a meta-analysis of five randomised controlled trials, including 2073 patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). We assessed survival endpoints, baseline comparability, and treatment intensity. Evidence Synthesis: [¹⁷⁷Lu]Lu-PSMA-617 significantly improved rPFS and PSA response. While modest overall, the OS benefit was more pronounced in taxane-naïve populations. Compared with Cabazitaxel, [¹⁷⁷Lu]Lu-PSMA-617 was associated with similar or better survival despite shorter treatment duration and potentially lower cumulative toxicity and cost. Economic modelling suggests it could offer a more sustainable therapeutic option under typical willingness-to-pay thresholds. Conclusions: [¹⁷⁷Lu]Lu-PSMA-617 shows clinical effectiveness and economic value in mCRPC, with potential advantages over Cabazitaxel and ARTA. Its use could be prioritised in early treatment lines. Patient Summary: This study suggests that PSMA-targeted radioligand therapy is at least as effective as other treatments for advanced prostate cancer, with potential benefits in terms of toxicity, duration, and overall cost. Full article

(This article belongs to the Special Issue Systematic Reviews and Meta-Analyses of Genitourinary Cancers (2nd Edition))

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20 pages, 8659 KiB

Open AccessArticle

Oncogenic Activity and Sorafenib Sensitivity of ARAF p.S214C Mutation in Lung Cancer

by Carol Lee, Weixue Mu, Xi July Chen, Mandy Sze Man Chan, Zhishan Chen, Sai Fung Yeung, Helen Hoi Yin Chan, Sin Ting Chow, Ben Chi Bun Ko, David Wai Chan, William C. Cho, Vivian Wai Yan Lui and Stephen Kwok Wing Tsui

Cancers 2025, 17(13), 2246; https://doi.org/10.3390/cancers17132246 - 4 Jul 2025

Viewed by 363

Abstract

Background/Objectives: RAF pathway aberrations are one of the hallmarks of lung cancer. Sorafenib is a multi-kinase inhibitor targeting the RAF pathway and is FDA-approved for several cancers, yet its efficacy in lung cancer is controversial. Previous clinical research showed that a [...] Read more.

Background/Objectives: RAF pathway aberrations are one of the hallmarks of lung cancer. Sorafenib is a multi-kinase inhibitor targeting the RAF pathway and is FDA-approved for several cancers, yet its efficacy in lung cancer is controversial. Previous clinical research showed that a ARAF p.S214C mutation exhibited exceptional responsiveness to sorafenib in lung adenocarcinoma. Methods: Considering this promising clinical potential, the oncogenic potential and sorafenib response of the ARAF p.S214C mutation were investigated using lung cancer models. ARAF p.S214C mutant, ARAF wild-type (WT), and EGFP control genes were ectopically expressed in lung adenocarcinoma cell lines retroviral transduction. In vitro and in vivo sorafenib sensitivity studies were performed, followed by transcriptomics and proteomics analyses. Results: Compared to the ARAF-WT and EGFP-engineered cells, the ARAF p.S214C-engineered cells activated Raf-MEK-ERK signaling and exhibited enhanced oncogenic potential in terms of in vitro cell proliferation, colony and spheroid formation, migration, and invasion abilities, as well as in vivo tumorigenicity. The ARAF p.S214C-engineered cells also displayed heightened sensitivity to sorafenib in vitro and in vivo. RNA sequencing and reverse-phase protein array analyses demonstrated elevated expression of genes and proteins associated with tumor aggressiveness in the ARAF p.S214C mutants, and its sorafenib sensitivity was likely moderated through inhibition of the cell cycle and DNA replication. The ERK and PI3K signaling pathways were also significantly deregulated in the ARAF p.S214C mutants regardless of sorafenib treatment. Conclusions: This study demonstrates the oncogenicity and sorafenib sensitivity of the ARAF p.S214C mutation in lung cancer cells, which may serve as a biomarker for predicting the sorafenib response in lung cancer patients. Importantly, investigating the gene–drug sensitivity pairs in clinically exceptional responders may guide and accelerate personalized cancer therapies based on specific tumor mutations. Full article

(This article belongs to the Section Cancer Therapy)

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16 pages, 529 KiB

Open AccessSystematic Review

Osteopontin Expression and Its Role in Endometrial Cancer: A Systematic Review

by Carmen Imma Aquino, Sakthipriyan Venkatesan, Arianna Ligori, Raffaele Tinelli, Elena Grossini and Daniela Surico

Cancers 2025, 17(13), 2245; https://doi.org/10.3390/cancers17132245 - 4 Jul 2025

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Abstract

Background/Objectives: Osteopontin (OPN) is a 34 kDa protein that is extensively phosphorylated and rich in aspartic acid, produced by a single-copy gene, and altered by post-translational processes. In several diseases, OPN has been discovered to play a direct role in immunological and inflammatory [...] Read more.

Background/Objectives: Osteopontin (OPN) is a 34 kDa protein that is extensively phosphorylated and rich in aspartic acid, produced by a single-copy gene, and altered by post-translational processes. In several diseases, OPN has been discovered to play a direct role in immunological and inflammatory responses. It is also important in kidney stone disease, preeclampsia, cardiovascular disease, endometriosis, and cancer, among other pathological conditions. It is a crucial extracellular matrix molecule involved in oncology, due to its ability to bridge the gap between inflammation and carcinogenesis. Methods: Our systematic review has as PICO “Does Osteopontin have possible etiological and prognostic correlations in patients affected by endometrial carcinoma?” Based on online data collected from PubMed, Scholar, Embase, Scopus, and other sources, a preliminary analysis was conducted. A keyword search for “Osteopontin” AND “tumors”, “endometrial cancer”, and other related terms was used to identify the publications. The relevance of scientific research was used to select articles in English. Results: For our systematic review, the citation search yielded nine articles on the topic. At the endometrial level, OPN plays a role in a variety of biological processes, including angiogenesis, metastasis, altered tissue remodeling, immunological responses, cell adhesion, and migration. Conclusions: With established direct correlations and a potential role in the assessment of the diagnosis and prognosis of the disease, OPN participates in endometrial cancer, drawing more and more attention from researchers. Full article

(This article belongs to the Special Issue Endometrial Cancer—Diagnosis and Treatment)

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27 pages, 890 KiB

Open AccessReview

Emerging Techniques of Translational Research in Immuno-Oncology: A Focus on Non-Small Cell Lung Cancer

by Mora Guardamagna, Eduardo Zamorano, Victor Albarrán-Artahona, Andres Mesas and Jose Carlos Benitez

Cancers 2025, 17(13), 2244; https://doi.org/10.3390/cancers17132244 - 4 Jul 2025

Viewed by 696

Abstract

The advent of personalized medicine and novel therapeutic strategies has transformed the treatment landscape of non-small cell lung cancer (NSCLC), significantly improving patient survival. However, only a minority of patients experience a durable benefit, as intrinsic or acquired resistance remains a major challenge. [...] Read more.

The advent of personalized medicine and novel therapeutic strategies has transformed the treatment landscape of non-small cell lung cancer (NSCLC), significantly improving patient survival. However, only a minority of patients experience a durable benefit, as intrinsic or acquired resistance remains a major challenge. Understanding the complex mechanisms of resistance—linked to tumor biology, the tumor microenvironment (TME), and host factors—is crucial to overcoming these barriers. Recent innovations in diagnostics, including artificial intelligence and liquid biopsy, offer promising tools to refine therapeutic decisions. Machine Learning and Deep Learning provide predictive algorithms that enhance diagnostic accuracy and prognostic assessment. Techniques like single-cell RNA sequencing and pathomics offer deeper insights into the role of the TME. Liquid biopsy, as a minimally invasive method, enables real-time detection of circulating tumor components, facilitating the identification of predictive and prognostic biomarkers and illuminating tumor heterogeneity. These translational research advances are revolutionizing the understanding of cancer biology and are key to optimizing personalized treatment strategies. This review highlights emerging tools aimed at improving diagnostic and therapeutic precision in NSCLC, underscoring their role in decoding the interplay between tumor cells, the TME, and the host to ultimately improve patient outcomes. Full article

(This article belongs to the Section Cancer Immunology and Immunotherapy)

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29 pages, 1939 KiB

Open AccessReview

Peroxisomal Alterations in Prostate Cancer: Metabolic Shifts and Clinical Relevance

by Mohamed A. F. Hussein, Celien Lismont, Hongli Li, Ruizhi Chai, Frank Claessens and Marc Fransen

Cancers 2025, 17(13), 2243; https://doi.org/10.3390/cancers17132243 - 4 Jul 2025

Viewed by 647

Abstract

Cancer is hallmarked by uncontrolled cell proliferation and enhanced cell survival, driven by a complex interplay of factors—including genetic and epigenetic changes—that disrupt metabolic and signaling pathways and impair organelle function. While the roles of mitochondria and the endoplasmic reticulum in cancer are [...] Read more.

Cancer is hallmarked by uncontrolled cell proliferation and enhanced cell survival, driven by a complex interplay of factors—including genetic and epigenetic changes—that disrupt metabolic and signaling pathways and impair organelle function. While the roles of mitochondria and the endoplasmic reticulum in cancer are widely recognized, emerging research is now drawing attention to the involvement of peroxisomes in tumor biology. Peroxisomes are essential for lipid metabolism, including fatty acid α- and β-oxidation, the synthesis of docosahexaenoic acid, bile acids, and ether lipids, as well as maintaining redox balance. Despite their critical functions, the role of peroxisomes in oncogenesis remains inadequately explored. Prostate cancer (PCa), the second most common cancer in men worldwide, exhibits a unique metabolic profile compared to other solid tumors. In contrast to the glycolysis-driven Warburg effect, primary PCa relies primarily on lipogenesis and oxidative phosphorylation. Peroxisomes are intricately involved in the metabolic adaptations of PCa, influencing both disease progression and therapy resistance. Key alterations in peroxisomal activity in PCa include the increased oxidation of branched-chain fatty acids, upregulation of α-methylacyl coenzyme A racemase (a prominent PCa biomarker), and downregulation of 1-alkyl-glycerone-3-phosphate synthase and catalase. This review critically examines the role of peroxisomes in PCa metabolism, progression, and therapeutic response, exploring their potential as biomarkers and targets for therapy. We also consider their relationship with androgen receptor signaling. A deeper understanding of peroxisome biology in PCa could pave the way for new therapies to improve patient outcomes. Full article

(This article belongs to the Special Issue Advancements in Molecular Research of Prostate Cancer)

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16 pages, 857 KiB

Open AccessArticle

Denosumab Dosage and Tooth Extraction Predict Medication-Related Osteonecrosis of the Jaw in Patients with Breast Cancer and Bone Metastases

by Suguru Yokoo, Shinichiro Kubo, Daisuke Yamamoto, Masahiko Ikeda, Tetsumasa Yamashita, Kumiko Yoshikawa, Hiroshi Mese and Sakiko Ohara

Cancers 2025, 17(13), 2242; https://doi.org/10.3390/cancers17132242 - 4 Jul 2025

Viewed by 446

Abstract

Background/Objectives: Prolonged use of denosumab in patients with metastatic breast cancer has raised concerns about the development of medication-related osteonecrosis of the jaw (MRONJ). However, the threshold at which the risk increases remains unclear. Methods: This retrospective cohort study analyzed patients [...] Read more.

Background/Objectives: Prolonged use of denosumab in patients with metastatic breast cancer has raised concerns about the development of medication-related osteonecrosis of the jaw (MRONJ). However, the threshold at which the risk increases remains unclear. Methods: This retrospective cohort study analyzed patients with breast cancer and bone metastases who received denosumab between May 2012 and August 2024. Associations between cumulative denosumab administration and MRONJ were evaluated using univariate and multivariate logistic regression analyses. A receiver operating characteristic (ROC) analysis was used to determine the optimal cutoff for cumulative doses. Results: MRONJ developed in 101 patients (31.2%). Multivariate analysis identified cumulative denosumab administration (odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.03–1.06; p < 0.001) and a history of tooth extraction (OR: 4.40, 95% CI: 2.23–8.71; p < 0.001) as independent risk factors for MRONJ. ROC analysis determined an optimal cutoff of 32 cumulative doses, with an area under the curve of 0.83 (95% CI: 0.78–0.88; p < 0.0001). Conclusions: Cumulative denosumab administration and history of tooth extraction were independent risk factors for MRONJ in patients with breast cancer and bone metastases. The risk of MRONJ increased after 32 cumulative doses, providing a clinically actionable threshold for risk assessment and patient monitoring. Full article

(This article belongs to the Section Cancer Metastasis)

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19 pages, 500 KiB

Open AccessArticle

Splenectomy in Onco-Hematologic Patients: A Retrospective Study of Early Complications and 1-Year Mortality

by Marion Faucher, Stanislas Ravot, Loïc Barthes, Jean Manuel de Guibert, Laurent Chow-Chine, Frédéric Gonzalez, Magali Bisbal, Luca Servan, Marie Tezier, Maxime Tourret, Sylvie Cambon, Camille Pouliquen, Damien Mallet, Lam Nguyen Duong, Florence Ettori, Jacques Ewald, Marc Léone, Antoine Sannini, Jonathan Garnier and Djamel Mokart

Cancers 2025, 17(13), 2241; https://doi.org/10.3390/cancers17132241 - 4 Jul 2025

Viewed by 339

Abstract

Background: Splenectomy remains necessary in selected oncologic and hematologic indications but is associated with significant postoperative morbidity and mortality. The data on outcomes in this high-risk population remain limited, particularly in mixed cohorts. Methods: We conducted a retrospective cohort study including all [...] Read more.

Background: Splenectomy remains necessary in selected oncologic and hematologic indications but is associated with significant postoperative morbidity and mortality. The data on outcomes in this high-risk population remain limited, particularly in mixed cohorts. Methods: We conducted a retrospective cohort study including all patients undergoing splenectomy for oncologic or hematologic causes between 2009 and 2022 at a cancer referral center. The primary outcomes were the occurrence of major complications at day 90 and the 1-year all-cause mortality. Multivariate logistic regression was used to identify independent predictors. Results: Among the 8503 ICU admissions from surgical wards, 204 splenectomies were performed; 179 patients were analyzed. The median age was 64 years, and 100 patients (55.9%) were female. Splenectomy was performed for hematologic malignancies in 76 cases (42.5%) and for oncologic causes in 103 cases (57.5%). Laparotomy was used in 154 cases (86.0%), and metastasectomy was performed in 54 patients (30.2%). At day 90, 86 patients (48.0%) developed a major complication: 12 deaths (6.7%), 44 surgical complications (24.6%), and 71 episodes of sepsis (39.7%). In a multivariate analysis, weight loss (OR 3.39, 95% CI [1.32–8.70], p = 0.011), laparotomy (OR 4.38 [1.09–17.60], p = 0.038), and a higher SAPS II score (OR 1.08 per point [1.03–1.13], p = 0.003) were associated with complications, while metastasectomy was protective (OR 0.23 [0.08–0.67], p = 0.007). At one year, the mortality reached 22.4%. Independent predictors of death were sepsis at one year (OR 5.04, 95% CI [1.30–25.96], p = 0.029), the Charlson Comorbidity Index (OR 1.30 per point, 95% CI [1.04–1.68], p = 0.030), invasive mechanical ventilation (OR 14.94, 95% CI [2.83–118.93], p = 0.003), and a performance status >1 (OR 7.84, 95% CI [2.38–27.75], p < 0.001). Encapsulated bacteria were not isolated; sepsis was mainly due to Gram-negative and enterococcal organisms. Conclusions: Splenectomy in onco-hematologic patients is associated with high rates of sepsis and mortality. In addition to surgical factors, frailty, immune status, and infection independently contribute to the patients’ outcomes. These results support risk-adapted perioperative strategies and long-term infectious surveillance in immunocompromised patients. Full article

(This article belongs to the Special Issue Perioperative Management and Cancer Outcome)

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20 pages, 308 KiB

Open AccessReview

Solid Pseudopapillary Neoplasm of the Pancreas: A Comprehensive Review Focusing on the Role of Endoscopic Ultrasound-Guided Radiofrequency Ablation as an Alternative Treatment

by Tawfik Khoury, Moaad Farraj, Wisam Sbeit, Andrea Lisotti and Bertrand Napoléon

Cancers 2025, 17(13), 2240; https://doi.org/10.3390/cancers17132240 - 4 Jul 2025

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Abstract

Background: Solid pseudopapillary neoplasm (SPN) is a rare pancreatic tumor with malignant potential. Its diagnosis has grown alongside increased use of abdominal imaging. SPN is suspected after classical findings in abdominal imaging studies; however, endoscopic ultrasound-guided (EUS) fine needle aspiration can support preoperative [...] Read more.

Background: Solid pseudopapillary neoplasm (SPN) is a rare pancreatic tumor with malignant potential. Its diagnosis has grown alongside increased use of abdominal imaging. SPN is suspected after classical findings in abdominal imaging studies; however, endoscopic ultrasound-guided (EUS) fine needle aspiration can support preoperative diagnosis. The treatment of choice is still surgical intervention, with an intent to reach curative resection. The prognosis is excellent. Recently, emerging data on EUS-guided radiofrequency ablation (RFA) suggest changing the choice of treatment for small SPN. Methods: We provide a comprehensive overview on pancreatic SPN with a focus on treatment, adverse events, recurrence rate, and outcomes. In addition, we provide a literature summary and pool data analysis. Results: Overall, 70 papers including 6651 patients were identified. The mean SPN size was 5.8 cm, metastasis rate was 1.9%, and recurrence rate was 3%. Moreover, the mortality rate was low at 0.2%, although high postoperative adverse events were reported (32.4%). Small SPN (<2 cm) was present in 4.1% of the studies. Two studies reported EUS-RFA for small SPN <2 cm, without recurrence at a median follow-up of 18.5 months. Conclusions: SPN still necessitates surgical intervention given its malignant potential. However, EUS-RFA can represent a promising and safe therapeutic option for SPN < 2 cm. Full article

(This article belongs to the Collection Targeting Solid Tumors)

28 pages, 1101 KiB

Open AccessReview

Next-Generation Therapies in Mantle Cell Lymphoma (MCL): The Evolving Landscape in Treatment of Relapse/Refractory After CAR-T Cells

by Elia Boccellato, Lorenzo Comba, Rita Tavarozzi, Claudia Castellino, Myriam Foglietta, Daniele Mattei, Marco Ladetto, Massimo Massaia and Alessia Castellino

Cancers 2025, 17(13), 2239; https://doi.org/10.3390/cancers17132239 - 3 Jul 2025

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Abstract

Mantle cell lymphoma (MCL) is a rare but heterogeneous subtype of non-Hodgkin lymphoma (NHL) with a prognosis ranging from very favorable in indolent cases to a poor prognosis for more aggressive variants [...] Full article

(This article belongs to the Special Issue Monoclonal Antibodies in Lymphoma)

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30 pages, 1826 KiB

Open AccessReview

Role of Human Microbiome in Development and Management of Head and Neck Squamous Cell Carcinoma

by Martin Palkovsky, Nikol Modrackova, Vera Neuzil-Bunesova, Marian Liberko, Alzbeta Hlodakova and Renata Soumarova

Cancers 2025, 17(13), 2238; https://doi.org/10.3390/cancers17132238 - 3 Jul 2025

Viewed by 1039

Abstract

Despite decades of research, cancer remains a major global health problem [...] Full article

(This article belongs to the Collection Advances in Diagnostics and Treatment of Head and Neck Cancer)

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Cancers, Volume 17, Issue 13 (July-1 2025) – 209 articles

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