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Volume 17
Issue 19
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Cancers, Volume 17, Issue 19 (October-1 2025) – 185 articles

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23 pages, 8340 KB  
Article
Chemotherapy Liberates a Broadening Repertoire of Tumor Antigens for TLR7/8/9-Mediated Potent Antitumor Immunity
by Cheng Zu, Yiwei Zhong, Shuting Wu and Bin Wang
Cancers 2025, 17(19), 3277; https://doi.org/10.3390/cancers17193277 - 9 Oct 2025
Viewed by 215
Abstract
Background: Most immunologically “cold” tumors do not respond durably to checkpoint blockade because tumor antigen (TA) release and presentation are insufficient to prime effective T-cell immunity. While prior work demonstrated synergy between cisplatin and a TLR7/8/9 agonist (CR108) in 4T1 tumors, the underlying [...] Read more.
Background: Most immunologically “cold” tumors do not respond durably to checkpoint blockade because tumor antigen (TA) release and presentation are insufficient to prime effective T-cell immunity. While prior work demonstrated synergy between cisplatin and a TLR7/8/9 agonist (CR108) in 4T1 tumors, the underlying mechanism—particularly whether chemotherapy functions as a broad antigen-releasing agent enabling TLR-driven immune amplification—remained undefined. Methods: Using murine models of breast (4T1), melanoma (B16-F10), and colorectal cancer (CT26), we tested multiple chemotherapeutic classes combined with CR108. We quantified intratumoral and systemic soluble TAs, antigen presentation and cross-priming by antigen-presenting cells, tumor-infiltrating lymphocytes, and cytokine production by flow cytometry/ICS. T-cell receptor β (TCRβ) repertoire dynamics in tumor-draining lymph nodes were profiled to assess amplitude and breadth. Tumor microenvironment remodeling was analyzed, and public datasets (e.g., TCGA basal-like breast cancer) were interrogated for expression of genes linked to TA generation/processing and peptide loading. Results: Using cisplatin + CR108 in 4T1 as a benchmark, we demonstrate that diverse chemotherapies—especially platinum agents—broadly increase the repertoire of soluble tumor antigens available for immune recognition. Across regimens, chemotherapy combined with CR108 increased T-cell recognition of candidate TAs and enhanced IFN-γ+ CD8+ responses, with platinum agents producing the largest expansions in soluble TAs. TCRβ sequencing revealed increased clonal amplitude without loss of repertoire breadth, indicating focused yet diverse antitumor T-cell expansion. Notably, therapeutic efficacy was not predicted by canonical damage-associated molecular pattern (DAMP) signatures but instead correlated with antigen availability and processing capacity. In human basal-like breast cancer, higher expression of genes involved in TA generation and antigen processing/presentation correlated with improved survival. Conclusions: Our findings establish an antigen-centric mechanism underlying chemo–TLR agonist synergy: chemotherapy liberates a broadened repertoire of tumor antigens, which CR108 then leverages via innate immune activation to drive potent, T-cell-mediated antitumor immunity. This framework for rational selection of chemotherapy partners for TLR7/8/9 agonism and support clinical evaluation to convert “cold” tumors into immunologically responsive disease. Full article
(This article belongs to the Special Issue Latest Breakthroughs in Tumor Immune Microenvironment: From Cellular Discovery to Cutting-Edge Technology)
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10 pages, 1467 KB  
Article
The Impact of Lymph Node Ratio for Children with Wilms Tumors: A National Cancer Database Analysis
by Ioannis A. Ziogas, Andrii Khomiak, Kaitlin E. Olson, Dimitrios P. Moris, Alexandria J. Robbins, Jenny Stevens, Shannon N. Acker, Jonathan P. Roach, Kristine S. Corkum and Nicholas G. Cost
Cancers 2025, 17(19), 3276; https://doi.org/10.3390/cancers17193276 - 9 Oct 2025
Viewed by 171
Abstract
Background: Lymph node status is a prognostic factor in Wilms tumor, and adequate lymph node sampling is strongly recommended. This study investigates the impact of lymph node ratio (LNR) (number of positive to examined lymph nodes) on overall survival in children with [...] Read more.
Background: Lymph node status is a prognostic factor in Wilms tumor, and adequate lymph node sampling is strongly recommended. This study investigates the impact of lymph node ratio (LNR) (number of positive to examined lymph nodes) on overall survival in children with resected Wilms tumors. Methods: This retrospective National Cancer Database analysis included children (<18 years) who underwent resection with lymph node sampling for unilateral, non-metastatic Wilms tumor. Results: Among 2206 patients, the median age was three years, the median tumor size was 10.5 cm, and the median number of examined nodes was five. A total of 82.1% of patients had an LNR of 0, 5.4% had an LNR < 0.2, and 12.5% had an LNR ≥ 0.2. In multivariable Cox regression, LNR ≥ 0.2 was associated with worse survival (HR = 1.75, 95%CI: 1.03–2.97, p = 0.04), along with increasing age (HR = 1.11, 95%CI: 1.05–1.17, p < 0.001) and tumor size (HR = 1.03, 95%CI: 1.00–1.06, p = 0.03). Conclusions: LNR is an independent prognostic factor in Wilms tumor and may refine risk stratification and guide treatment decisions. Full article
(This article belongs to the Section Cancer Pathophysiology)
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20 pages, 1465 KB  
Review
The Genomic Topography of Appendiceal Cancers: Our Current Understanding, Clinical Perspectives, and Future Directions
by Daniel J. Gironda, Richard A. Erali, Steven D. Forsythe, Ashok K. Pullikuth, Rui Zheng-Pywell, Kathleen A. Cummins, Shay Soker, Xianyong Gui, Edward A. Levine, Konstantinos I. Votanopoulos and Lance D. Miller
Cancers 2025, 17(19), 3275; https://doi.org/10.3390/cancers17193275 - 9 Oct 2025
Viewed by 399
Abstract
Background/Objectives: Appendiceal cancer (AC) is a rare and understudied malignancy with limited genomic data available to guide clinical interventions. Historically treated as a subtype of colorectal cancer, AC is now recognized as a distinct disease with unique histologic subtypes and molecular features. [...] Read more.
Background/Objectives: Appendiceal cancer (AC) is a rare and understudied malignancy with limited genomic data available to guide clinical interventions. Historically treated as a subtype of colorectal cancer, AC is now recognized as a distinct disease with unique histologic subtypes and molecular features. This review aims to consolidate current genomic data across AC subtypes and explore the clinical relevance of recurrent mutations. Methods: A systematic literature review was performed in accordance with general Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. Using search engines such as PubMed and Web of Science, we selected studies based on relevance to AC genomics using search terms such as “appendix cancer”, “appendiceal cancer”, “pseudomyxoma peritonei”, “sequencing”, “mutation”, and “genotype”. Results: AC comprises five major histologic subtypes—appendiceal neuroendocrine neoplasms (ANENs), mucinous appendiceal neoplasms (MANs), goblet cell adenocarcinomas (GCAs), colonic-type adenocarcinomas (CTAs) and signet ring cell adenocarcinomas (SRCs)—each with unique clinical behaviors and mutational profiles. Low-grade tumors, such as ANENs and MANs, frequently harbor KRAS and GNAS mutations, while high-grade subtypes, such as CTAs and SRCs, are enriched for TP53, APC, and SMAD gene alterations. GCA tumors exhibit a distinct mutational spectrum involving chromatin remodeling genes such as ARID1A and KMT2D. Compared to colorectal cancer, AC demonstrates lower frequencies of APC and TP53 mutations and a higher prevalence of GNAS mutations, consistent with a pathological divergence from CRC. Conclusions: The genomic heterogeneity of AC is commensurate with its histological complexity and has important implications for diagnosis, prognosis and treatment. While certain actionable mutations are present in a subset of tumors, large-scale genomic characterization efforts and development of subtype-specific models will be essential for advancing precision medicine in AC. Full article
(This article belongs to the Special Issue Rare Cancers, Diagnostic Challenges and Personalized Therapeutic Approaches in the 21st Century (2nd Edition))
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16 pages, 773 KB  
Article
Implementing a Geriatric Assessment-Guided Rehabilitation Care Model in Community Oncology Care: Feasibility and Impact on Patient-Reported and Performance-Based Outcomes
by Mackenzi Pergolotti, Kelley C. Wood, Mary Hidde, Tiffany D. Kendig, Deanna Meehan, Katie Hutzayluk, Alaina M. Newell, Jessica Bertram, Ashley Lightner, Stacye Mayo, Alina Hedaya, Smith Giri and Grant R. Williams
Cancers 2025, 17(19), 3274; https://doi.org/10.3390/cancers17193274 - 9 Oct 2025
Viewed by 216
Abstract
Background: Adults with cancer who are pre-frail or frail are at risk of poor outcomes. Geriatric assessment (GA) is recommended to assess and manage vulnerability and risk of frailty in older adults with cancer (≥65) and to inform referrals in supportive services, including [...] Read more.
Background: Adults with cancer who are pre-frail or frail are at risk of poor outcomes. Geriatric assessment (GA) is recommended to assess and manage vulnerability and risk of frailty in older adults with cancer (≥65) and to inform referrals in supportive services, including rehabilitation. Yet, adoption of the GA in community oncology practice lags, and frailty among adults younger than 65 often goes undetected and/or unaddressed. We evaluated the feasibility of a GA-guided rehabilitation care model and assessed changes in patient-reported and performance-based outcomes after rehabilitation. Methods: Adults (≥18 years) starting systemic therapy at a community oncology practice enrolled in the study. The GA was administered online and monthly for one year. Frailty/pre-frailty was identified using a previously validated 44-item index. The oncology team was notified of frail/pre-frail patients and then made referrals to outpatient rehabilitation. Feasibility outcomes (recruitment, retention, fidelity) and participant acceptability [7 items, 0–5 Likert scale] were analyzed descriptively. Patient-reported and performance-based outcomes were examined using the paired t-test. Results: 48% of eligible patients enrolled (N = 141), and 83% completed at least one GA. Frailty/pre-frailty was identified in 40% of the GAs, resulting in 282 referrals to rehabilitation (99% fidelity). Acceptability scores ranged from 3.5 ± 1.7 to 4.7 ± 0.6. Participants who attended rehabilitation (52%) improved significantly in outcomes measuring health-related quality of life, mobility, aerobic capacity, and strength (all p < 0.05). Conclusion: Implementing a GA-guided rehabilitation care model was feasible and acceptable to patients receiving systemic treatment. Those who attended rehabilitation experienced significant improvement in patient-reported and performance-based outcomes. Full article
(This article belongs to the Special Issue Treatment Outcomes in Older Adults with Cancer)
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19 pages, 969 KB  
Article
The Prognostic Role of Geriatric Nutritional Risk Index in Periampullary Cancer Patients Undergoing Pancreaticoduodenectomy: A Propensity Score-Matched Survival Study
by Chih-Ying Li, Wei-Feng Li, Yueh-Wei Liu, Yu-Yin Liu, Cheng-Hsi Yeh, Yu-Hung Lin, Jen-Yu Cheng and Shih-Min Yin
Cancers 2025, 17(19), 3273; https://doi.org/10.3390/cancers17193273 - 9 Oct 2025
Viewed by 150
Abstract
Background: The Geriatric Nutritional Risk Index (GNRI) is a simple tool for nutritional assessment, but its long-term prognostic value in patients undergoing pancreaticoduodenectomy (PD) remains unclear. Methods: This retrospective study included adult patients who underwent PD between January 2014 and December 2023 [...] Read more.
Background: The Geriatric Nutritional Risk Index (GNRI) is a simple tool for nutritional assessment, but its long-term prognostic value in patients undergoing pancreaticoduodenectomy (PD) remains unclear. Methods: This retrospective study included adult patients who underwent PD between January 2014 and December 2023 at Chang Gung Memorial Hospital. Patients were grouped by GNRI: inferior (<82), moderate (82–98), and superior (≥98). Propensity score matching was performed based on age, sex, cancer type, surgical approach, and ASA status. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS). Results: Among 371 patients, inferior GNRI was associated with worse median survival time (18.64 vs. 34.62 months, HR = 2.953, p < 0.001). This association was observed in both pancreatic cancer and other periampullary malignancies. Inferior GNRI also correlated with higher short-term mortality and adverse perioperative outcomes, including longer ICU stay, and greater need for ventilator support, reintubation, reoperation and total parenteral nutrition (TPN). Conclusions: Preoperative GNRI is a strong predictor of survival and short-term outcomes in PD patients. Early nutritional assessment may aid risk stratification and intervention. Full article
(This article belongs to the Section Methods and Technologies Development)
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23 pages, 729 KB  
Review
Immune Checkpoint Inhibitors in Merkel Cell Carcinoma of the Skin: A 2025 Comprehensive Review
by Patricia Tai, Omar Alqaisi, Suhair Al-Ghabeesh, Lorent Sijarina, Edward Yu, Aoife Jones Thachuthara, Avi Assouline, Osama Souied, Kimberly Hagel and Kurian Joseph
Cancers 2025, 17(19), 3272; https://doi.org/10.3390/cancers17193272 - 9 Oct 2025
Viewed by 737
Abstract
Objective: Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. Although immunotherapy has transformed MCC management, published data remain limited. This comprehensive review evaluates current evidence on immune checkpoint inhibitors (ICIs) in MCC, in relation to other treatment modalities [...] Read more.
Objective: Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. Although immunotherapy has transformed MCC management, published data remain limited. This comprehensive review evaluates current evidence on immune checkpoint inhibitors (ICIs) in MCC, in relation to other treatment modalities such as surgery and radiotherapy. Methods: Peer-reviewed articles published between January 2000 and August 2025 were searched manually in four databases: Scopus, ScienceDirect, PubMed and MEDLINE, using the keywords “Merkel cell carcinoma” AND “immunotherapy” AND “immune checkpoint inhibitors”. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology was employed. Results: ICIs can be given in different settings: (A) Neoadjuvant: The CheckMate 358 trial reported a 54.5% response rate among 33 radiologically evaluable patients treated with nivolumab, each showing over 30% tumor reduction. (B) Adjuvant: (1) The ADMEC-O phase II trial demonstrated improved disease-free survival with adjuvant nivolumab. (2) The ADAM phase III trial evaluates adjuvant avelumab in node-positive patients post-surgery/radiation, with common side effects including nausea, fatigue, and itching. (3) STAMP, a phase III trial, investigates pembrolizumab in stage I–III MCC. Both ADAM and STAMP have completed accrual and results are pending. (C) Primary therapy: KEYNOTE-017 and JAVELIN trials reported a 60% overall response rate and ~40% 3-year progression-free survival with first-line pembrolizumab or avelumab. Both agents also show promise as salvage therapies. Conclusions: ICIs demonstrate encouraging outcomes in MCC across various treatment stages. Continued research is essential to optimize treatment timing and integrate multimodal therapies. Full article
(This article belongs to the Special Issue Combination Immunotherapy for Cancer Treatment)
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16 pages, 5548 KB  
Article
RNF135 Expression Marks Chemokine (C-C Motif) Ligand-Enriched Macrophage–Tumor Interactions in the Glioblastoma Microenvironment
by Jianan Chen, Qiong Wu, Anders E. Berglund, Robert J. Macaulay, James J. Mulé and Arnold B. Etame
Cancers 2025, 17(19), 3271; https://doi.org/10.3390/cancers17193271 - 9 Oct 2025
Viewed by 191
Abstract
Background: Tumor-associated macrophages (TAMs) are essential regulators of the glioblastoma (GBM) microenvironment; their functional heterogeneity and interaction networks are not fully elucidated. We identify RNF135 as a novel TAM-enriched gene associated with immune activation and adverse prognosis in GBM. Methods: To evaluate RNF135 [...] Read more.
Background: Tumor-associated macrophages (TAMs) are essential regulators of the glioblastoma (GBM) microenvironment; their functional heterogeneity and interaction networks are not fully elucidated. We identify RNF135 as a novel TAM-enriched gene associated with immune activation and adverse prognosis in GBM. Methods: To evaluate RNF135’s expression profile, prognostic significance, and functional pathways, extensive transcriptome analyses from TCGA and CGGA cohorts were conducted. The immunological landscape and cellular origin of RNF135 were outlined using single-cell RNA-seq analyses and bulk RNA-seq immune deconvolution (MCP-counter, xCell and ssGSEA). Cell–cell communication networks between tumor cells and RNF135-positive and -negative tumor-associated macrophage subsets were mapped using CellChat. Results: RNF135 predicted a poor overall survival and was markedly upregulated in GBM tissues. Functional enrichment analyses showed that increased cytokine signaling, interferon response, and innate immune activation were characteristics of RNF135-high samples. Immune infiltration profiling showed a strong correlation between the abundance of T cells and macrophages and RNF135 expression. According to the single-cell analyses, RNF135 was primarily expressed in TAMs, specifically in proliferation, phagocytic, and transitional subtypes. RNF135-positive TAMs demonstrated significantly improved intercellular communication with aggressive tumor subtypes in comparison to RNF135-negative TAMs. This was facilitated by upregulated signaling pathways such as MHC-II, CD39, ApoE, and most notably, the CCL signaling axis. The CCL3/CCL3L3–CCR1 ligand–receptor pair was identified as a major mechanistic driver of TAM–TAM crosstalk. High RNF135 expression was also linked to greater sensitivity to Selumetinib, a selective MEK1/2 inhibitor that targets the MAPK/ERK pathway, according to drug sensitivity analysis. Conclusions: RNF135 defines a TAM phenotype in GBM that is both immunologically active and immunosuppressive. This phenotype promotes inflammatory signaling and communication between cells in the tumor microenvironment. Targeting the CCL–CCR1 axis or combining RNF135-guided immunomodulation with certain inhibitors could be a promising therapeutic strategies for GBM. Full article
(This article belongs to the Special Issue Molecular Genomics in Brain Tumors)
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22 pages, 703 KB  
Systematic Review
Current Perspectives on Non-Metastatic Male Breast Cancer: Genetics, Biology, and Treatment Advances: A Systematic Review
by Kathleen Melan, Pierre Loap and Youlia Kirova
Cancers 2025, 17(19), 3270; https://doi.org/10.3390/cancers17193270 - 9 Oct 2025
Viewed by 336
Abstract
Background/Objectives: Male breast cancer (MBC) is a rare malignancy representing less than 1% of all breast cancer cases, with rising incidence worldwide. Current treatment strategies largely rely on extrapolation from female breast cancer, despite clear biological and clinical distinctions. This review aims to [...] Read more.
Background/Objectives: Male breast cancer (MBC) is a rare malignancy representing less than 1% of all breast cancer cases, with rising incidence worldwide. Current treatment strategies largely rely on extrapolation from female breast cancer, despite clear biological and clinical distinctions. This review aims to summarize current knowledge on non-metastatic MBC, with a particular focus on genetic predisposition, tumor biology, and recent therapeutic advances. Methods: A systematic literature search was conducted using PubMed and PMC databases to identify clinical trials, observational studies and systematic reviews related to MBC published up to 1st June, 2025. Studies were selected for their relevance to genetic and molecular features, as well as treatment outcomes in non-metastatic disease. Results: Fifty-one studies were included in the review. Findings confirm the predominance of hormone receptor–positive tumors in MBC and underscore the central role of BRCA2 mutations. Germline mutations in BRCA2 and BRCA1 were reported in approximately 1 and 2% of male cases, respectively. Additional germline alterations were identified in PALB2, CHEK2, and other DNA repair genes. Comparative analyses of surgical approaches showed no significant difference in survival between breast-conserving surgery and mastectomy. Postmastectomy radiotherapy improved overall survival compared to surgery alone. Adjuvant tamoxifen therapy was independently associated with significant survival benefits, although adherence remains a challenge. Conclusions: MBC is a biologically distinct and molecularly heterogeneous disease. Breast-conserving surgery appears safe and effective in selected patients. Adjuvant radiotherapy and tamoxifen confer clear survival advantages. The lack of male-specific clinical trials remains a major limitation in optimizing evidence-based care for MBC. Full article
(This article belongs to the Section Cancer Therapy)
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19 pages, 1208 KB  
Article
Local Recurrence After Nephron Surgery: What to Do? An Italian Multicentric Registry
by Angelo Porreca, Filippo Marino, Davide De Marchi, Marco Giampaoli, Daniele D’Agostino, Francesca Simonetti, Antonio Amodeo, Paolo Corsi, Francesco Claps, Alessandro Crestani, Riccardo Bertolo, Alessandro Antonelli, Fabrizio Di Maida, Andrea Minervini, Paolo Parma, Roberto Falabella, Stefano Zaramella, Francesco Greco, Maria Chiara Sighinolfi, Bernardo Rocco, Carmine Sciorio, Antonio Celia, Francesca Romana Prusciano, Pier Paolo Prontera, Gian Maria Busetto and Luca Di Gianfrancescoadd Show full author list remove Hide full author list
Cancers 2025, 17(19), 3269; https://doi.org/10.3390/cancers17193269 - 9 Oct 2025
Viewed by 249
Abstract
Introduction and Objectives: Local recurrence (LR) in patients treated with surgery for renal cell carcinoma (RCC) remains a significant clinical challenge that requires thorough investigation. Our study aimed to identify the relative risk factors and explore the optimal clinical management of LR. Materials [...] Read more.
Introduction and Objectives: Local recurrence (LR) in patients treated with surgery for renal cell carcinoma (RCC) remains a significant clinical challenge that requires thorough investigation. Our study aimed to identify the relative risk factors and explore the optimal clinical management of LR. Materials and Methods: We conducted a non-randomized, observational, retrospective multicentric registry involving multiple Italian urological centers. We included patients treated with surgery (either nephron-sparing or radical nephrectomy) who later developed LR, defined as recurrence in the ipsilateral kidney or renal fossa. Patients with hereditary syndromes or metastatic disease at the time of LR diagnosis were excluded. Results: We reported 135 cases of LR with the following characteristics: most primary lesions were monofocal (85.7%), with a median size of 42 mm (23–53), the median R.E.N.A.L. score was 7 (6–8), and the median Padua score was 7 (6–9). Patients were treated with robot-assisted techniques in 59% of cases, laparoscopic surgery in 32.4%, and open surgery in 8.6%. Nephron-sparing surgery was performed in 75.2% of cases. Ischemia occurred in 61% of the cases, with a median ischemia time of 21 min (15.5–24). Intraoperative complications occurred in 3.8% of cases, while postoperative complications were reported in 13.8%, all of which were grade ≤3 according to the Clavien–Dindo classification. The primary tumors were pT1a in 43.5% of cases, pT1b in 26.3%, pT2 in 14.7% and pT3 in 15.5%. Histologically, 84% of cases were clear cell, 11.3% papillary type 1 or 2, and 3.7% chromophobe. Sarcomatoid/rhabdoid variants were present in 10.5% of cases. The median rate of LR was 1.3% (range 0.2–3.6), while the median time to LR was 18 months (12–39). LR occurred in the ipsilateral kidney in 70.5% of cases and in the ipsilateral renal fossa in 29.5%. The median rate of PSM in LR cases at initial surgery was 2.4% (range 0–4.3), while the median rate of negative surgical margin (NSM) in LR cases at initial surgery was 0.1 (0–0.3). Following LR diagnosis, most patients (49.2%) underwent surgery, 29.1% received cryoablation or radiotherapy, 17.1% received systemic treatment alone, and 4.6% followed a watchful waiting/active surveillance approach. At a median follow-up of 62 months, the highest oncological control in terms of 5-year cancer-specific survival and overall survival rates was achieved in surgically treated patients. The PSM, the histological variant, and their combination were found to be independent variables correlated with the occurrence of LR, with relative risks of 3.62, 2.71, and 8.12, respectively. Conclusions: LR after nephron-sparing or radical nephrectomy represents a significant clinical dilemma. Known risk factors are not always sufficient to predict recurrence, emphasizing the necessity of consistent radiological follow-up per guideline recommendations. Early detection of recurrence and a multidisciplinary approach involving expert centers are crucial for optimizing patient outcomes. Full article
(This article belongs to the Special Issue Optimizing Surgical Procedures and Outcomes in Renal Cancer)
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18 pages, 392 KB  
Review
Advanced Biliary Tract Cancer: Exploration of Third-Line and Other Therapeutic Areas After Failure of Chemotherapy Alone
by Li Ma and Cheng Yi
Cancers 2025, 17(19), 3268; https://doi.org/10.3390/cancers17193268 - 9 Oct 2025
Viewed by 272
Abstract
Biliary tract cancer (BTC) is a highly aggressive malignancy with an extremely poor prognosis and a gradually increasing incidence, warranting increased clinical attention. The majority of BTC patients are diagnosed at an unresectable stage, making systemic therapy—including first-line and subsequent treatments—critical for outcomes. [...] Read more.
Biliary tract cancer (BTC) is a highly aggressive malignancy with an extremely poor prognosis and a gradually increasing incidence, warranting increased clinical attention. The majority of BTC patients are diagnosed at an unresectable stage, making systemic therapy—including first-line and subsequent treatments—critical for outcomes. However, due to disparities in medical resources and limited understanding of the disease, outcomes following first- and second-line therapies remain suboptimal. In this context, third-line treatment offers a potential opportunity to further extend patient survival, although challenges such as poor treatment tolerance and significant drug-related toxicities remain. A rational integration of chemotherapy, targeted therapy, immunotherapy, and novel radiotherapy techniques may constitute a standardized third-line therapeutic strategy for BTC. This review aims to discuss potential therapeutic adaptations and options in the setting where conventional chemotherapy has failed. Full article
(This article belongs to the Special Issue Recent Advances in Hepatobiliary Cancers: From Diagnosis to Treatment (2nd Edition))
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22 pages, 21528 KB  
Article
Prognostic Significance of CK5/6 and GATA3 Expression in Recurrent Urothelial Carcinoma
by Marzena Lenda-Petrykowska, Violetta Sulżyc-Bielicka, Wojciech Dobrzycki, Krzysztof Safranow, Jerzy Świtała, Dorota Kostrzewa-Nowak and Paweł Bielicki
Cancers 2025, 17(19), 3267; https://doi.org/10.3390/cancers17193267 - 9 Oct 2025
Viewed by 237
Abstract
Background/Objectives: The study aimed to determine whether the expression of CK5/6 and GATA3 is altered in UCa recurrences and to evaluate disease-free survival (DFS) and overall survival (OS) according to CK5/6 and GATA3 expression. Methods: A retrospective study was performed in 77 patients [...] Read more.
Background/Objectives: The study aimed to determine whether the expression of CK5/6 and GATA3 is altered in UCa recurrences and to evaluate disease-free survival (DFS) and overall survival (OS) according to CK5/6 and GATA3 expression. Methods: A retrospective study was performed in 77 patients with UCa. Surgery was performed in 35 patients. UCa recurrence was observed in 75% of patients. An immunohistochemical assessment of CK5/6 and GATA3 was performed in the primary and recurrent UCa groups. Results: CK5/6(+) in primary UCa was associated with a 73% probability of CK5/6(+) recurrence (p = 0.000005) and incidence at a younger age. CK5/6(−) in primary UCa was associated with an 84% probability of CK5/6(−) recurrence (p = 0.000005) and incidence at older age. A higher probability of UCa GATA3(+) recurrence was a significant independent factor associated with longer OS (p = 0.015). A greater probability of UCa CK5/6(+) recurrence was a significant independent factor associated with shorter OS (p = 0.044). Patients with CK5/6(+)-only UCa recurrences had significantly worse OS compared to UCa patients with at least one CK5/6(−) recurrence. Conclusions: 1. CK5/6 and GATA3 in UCa recurrences may differ from CK5/6 and GATA3 expression in primary UCa. Intensified oncological surveillance is suggested for patients with recurrent CK5/6(+) 2. Patients with at least one UCa CK5/6(−) recurrence have better prognosis compared to patients with only CK5/6(+) recurrences. Full article
(This article belongs to the Section Molecular Cancer Biology)
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18 pages, 617 KB  
Systematic Review
Movement-Based Interventions in Patients Affected by Bone Metastases: Impact on Physical Function and Functional Autonomy—A Systematic Review
by Giorgia Petrucci, Agnese Broccolo, Anna Marchetti, Chiara Monterosso, Giuseppe Casale, Chiara Timarco, Tea Zeppola, Silvia Dsoke, Elena Sandri, Michela Piredda, Giuseppe Francesco Papalia and Maria Grazia De Marinis
Cancers 2025, 17(19), 3266; https://doi.org/10.3390/cancers17193266 - 9 Oct 2025
Viewed by 301
Abstract
Background: Bone metastases are a common complication in patients with advanced cancer. These patients often experience a decline in physical function and autonomy, particularly in the ability to perform Activities of Daily Living, and structured movement-based interventions may represent an important supportive strategy. [...] Read more.
Background: Bone metastases are a common complication in patients with advanced cancer. These patients often experience a decline in physical function and autonomy, particularly in the ability to perform Activities of Daily Living, and structured movement-based interventions may represent an important supportive strategy. The aim of this study is to describe the available evidence regarding the impact of physical activity and exercise interventions on functional status and ADL performance in patients with bone metastases. Methods: A systematic literature review was conducted in PubMed, Scopus, Embase, Web of Science, and CINAHL database up to March 2025 and reported according to PRISMA guidelines. Eligible studies included adults (≥18 years) with confirmed bone metastases who underwent physical activity interventions designed to enhance functional status and ADLs. Studies’ methodological quality was assessed using the Joanna Briggs Institute critical appraisal tools, selected according to study design. Results: Eleven studies were included: four randomized controlled trials, four quasi-experimental studies, one randomized feasibility trial, one cross-sectional observational study, and one case report. Despite heterogeneity in intervention type, duration, and outcome measures, most studies reported improvements in physical function, including mobility, muscle strength, walking capacity, and endurance, as well as enhanced performance in ADLs and reductions in fatigue. No serious adverse events were reported. Conclusions: Structured physical activity appears safe and may improve function and independence in patients with bone metastases. These findings support the integration of individualized exercise programs into multidisciplinary supportive care. Full article
(This article belongs to the Special Issue Nursing and Supportive Care for Cancer Survivors)
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13 pages, 1016 KB  
Article
Clinical Predictors and Prognostic Significance of Pathologic Disease Upstaging at Radical Cystectomy in Patients with Muscle-Invasive Bladder Cancer
by Salvador Jaime-Casas, Wesley Yip, Daniel J. Lama, Vitor Goes, Miguel Zugman, Koral Shah, Regina Barragan-Carrillo, Hedyeh Ebrahimi, Daniela V. Castro, Yu Jun Li, Benjamin Mercier, JoAnn Hsu, Xiaochen Li, Clayton S. Lau, Kevin G. Chan, Bertram E. Yuh, Alexander Chehrazi-Raffle, Sumanta K. Pal and Abhishek Tripathi
Cancers 2025, 17(19), 3265; https://doi.org/10.3390/cancers17193265 - 9 Oct 2025
Viewed by 215
Abstract
Introduction: Staging inaccuracies in muscle-invasive bladder cancer (MIBC) can lead to undertreatment or overtreatment. We evaluated clinical and pathological predictors of pathologic upstaging (pUS) stratifying by neoadjuvant chemotherapy (NAC) receipt among patients undergoing robot-assisted radical cystectomy (RARC). Methods: We included patients with MIBC [...] Read more.
Introduction: Staging inaccuracies in muscle-invasive bladder cancer (MIBC) can lead to undertreatment or overtreatment. We evaluated clinical and pathological predictors of pathologic upstaging (pUS) stratifying by neoadjuvant chemotherapy (NAC) receipt among patients undergoing robot-assisted radical cystectomy (RARC). Methods: We included patients with MIBC (≥cT2N0M0) who underwent RARC from February 2004 through October 2020. Patients were grouped as (1) pUS with NAC, (2) pUS without NAC, and (3) no pUS (reference). Baseline characteristics were summarized using descriptive statistics. Logistic regression assessed the association between baseline characteristics and odds for upstaging. Kaplan–Meier method estimated overall survival (OS) and recurrence-free survival (RFS), and log-rank test compared the survival distribution between groups. Univariable and multivariable Cox regression models identified variables associated with OS and RFS. Results: Among 277 patients, 38.6% (n = 107) were upstaged with NAC (n = 37) or without NAC (n = 70). Most were male (79%), white (72%), and had cT2 stage (85%). Median age at surgery was 72 yrs. Preoperative hydronephrosis showed higher odds of upstaging [OR 2.24 (95% CI, 1.31–3.81), p = 0.003]. pUS with NAC [HR 1.99 (95% CI, 1.23–3.22), p = 0.005] and without NAC [HR 3.18 (95% CI, 2.21–4.55), p < 0.001] predicted worse OS (33.5 vs. 18.8 mos) compared to patients without pUS (135.3 mos). pUS with NAC [HR 2.49 (95% CI, 1.58–3.94) p < 0.001] and without NAC [HR 3.02 (95% CI 2.11–4.31), p < 0.001] predicted worse RFS. Conclusions: Preoperative hydronephrosis was the strongest predictor for pUS, independent of other baseline covariates. This highlights the need for better pre-operative risk stratification strategies for patients with MIBC undergoing RARC. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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15 pages, 3047 KB  
Article
From CT to Microscopy: Radiological–Histopathological Correlation for Understanding Abdominal Lymphomas
by Ante Luetić, Martina Luetić, Benjamin Benzon and Danijela Budimir Mršić
Cancers 2025, 17(19), 3264; https://doi.org/10.3390/cancers17193264 - 9 Oct 2025
Viewed by 264
Abstract
Background: Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of indolent or aggressive lymphoproliferative neoplasms arising from lymph nodes or in extranodal locations. Computed tomography (CT) is the imaging modality of choice, while the definitive diagnosis is confirmed by analyzing tissue samples. The aim [...] Read more.
Background: Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of indolent or aggressive lymphoproliferative neoplasms arising from lymph nodes or in extranodal locations. Computed tomography (CT) is the imaging modality of choice, while the definitive diagnosis is confirmed by analyzing tissue samples. The aim of this study was to determine the correlation between CT characteristics and histopathological types of abdominal lymphomas. Methods: A retrospective cross-sectional study included 119 patients with histopathologically confirmed abdominal lymphomas who underwent CT of the abdomen and pelvis prior to treatment. The following CT parameters were extracted: morphological presentation (enlarged lymph nodes/conglomerates, solid mass/masses, gastrointestinal wall thickening, abdominal organ involvement, intra- and extraperitoneal infiltrates), location, two-dimensional size, propagation if present, and postcontrast enhancement. Results: Enlarged lymph nodes were a slightly more common CT morphological appearance in the indolent B NHL group, while gastrointestinal (GI) wall thickening, solid masses, and infiltrates were more frequent in the aggressive B NHL group (p = 0.0256). Aggressive B-cell lymphomas had larger size at time of diagnosis compared to other types (p = 0.0436). CT postcontrast enhancement showed lymphomas originating from the gastrointestinal tract, which presented as wall thickening, had the highest enhancement (p = 0.0065 and p = 0.0485). Conclusions: Observed differences in abdominal lymphomas’ histopathological and imaging characteristics including location/origin, CT morphological appearance, and postcontrast enhancement revealed that extranodal lymphomas were more often of the aggressive B-cell type, aggressive B-cell types were larger, and GI tract lymphomas showed the most prominent enhancement. These findings can help in the diagnostic process and enable better management of lymphomas. Full article
(This article belongs to the Section Cancer Pathophysiology)
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11 pages, 517 KB  
Article
Understanding the Will Rogers Phenomenon in Cholangiocarcinoma Research and Beyond
by Ruslan Akhmedullin, Zhandos Burkitbayev, Tair Koishibayev, Zhanat Spatayev, Abylaikhan Sharmenov, Oxana Shatkovskaya, Dinara Zharlyganova, Almira Manatova, Zhuldyz Kuanysh, Sanzhar Shalekenov and Abduzhappar Gaipov
Cancers 2025, 17(19), 3263; https://doi.org/10.3390/cancers17193263 - 8 Oct 2025
Viewed by 194
Abstract
Background. The existing literature highlights a lack of comparative studies between subtypes of cholangiocarcinoma (CC) and the impact of misclassification on the epidemiological parameters. Methods. A retrospective study was conducted to evaluate the surgical outcomes. The authors used Poisson regression with modified errors [...] Read more.
Background. The existing literature highlights a lack of comparative studies between subtypes of cholangiocarcinoma (CC) and the impact of misclassification on the epidemiological parameters. Methods. A retrospective study was conducted to evaluate the surgical outcomes. The authors used Poisson regression with modified errors to calculate the risk ratios (RR) and reported post-estimation marginal effects. Coefficient estimates, variance inflation factors, and Pearson’s goodness-of-fit test statistics were used to check for multicollinearity and model fit, respectively. We also performed a reclassification analysis by modeling Klatskin tumors (PCC) as extrahepatic (ECC), reclassifying them as intrahepatic (ICC), and comparing the corresponding changes in estimates. Results. Regression analysis revealed an increased risk of death in patients with ICC (RR = 2.05, 95% CI 1.11–3.78) and PCC (RR = 2.03, 95% CI 0.97–4.24) compared to those with DCC. When PCC was analyzed as an ECC, the ICC revealed an RR of 1.52 (95% CI 0.84–2.73). Further reclassification of PCC showed an RR of 2.04 for ICC (95% CI: 1.53–3.53). The adjusted marginal effects saw a reduction in the death probability for both ICC and ECC. However, post hoc analyses revealed insufficient evidence for differences between the reclassified models. Conclusions. Patients with DCC had slightly better prognosis compared to ICC and PCC. We found no differences in survival between ICC and ECC (combining DCC and PCC). The decrease in mortality risk due to reclassification in both groups was not confirmed statistically. Future studies should focus on statistical evidence when referring to the Will Rogers phenomenon, instead of inferring from raw comparisons. Full article
(This article belongs to the Section Methods and Technologies Development)
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26 pages, 1116 KB  
Review
Optimizing Anti-PD1 Immunotherapy: An Overview of Pharmacokinetics, Biomarkers, and Therapeutic Drug Monitoring
by Joaquim Faria Monteiro, Alexandrina Fernandes, Diogo Gavina Tato, Elias Moreira, Ricardo Ribeiro, Henrique Reguengo, Jorge Gonçalves and Paula Fresco
Cancers 2025, 17(19), 3262; https://doi.org/10.3390/cancers17193262 - 8 Oct 2025
Viewed by 466
Abstract
Anti-PD-1 therapies have transformed cancer treatment by restoring antitumor T cell activity. Despite their broad clinical use, variability in treatment response and immune-related adverse events underscore the need for therapeutic optimization. This article provides an integrative overview of the pharmacokinetics (PKs) of anti-PD-1 [...] Read more.
Anti-PD-1 therapies have transformed cancer treatment by restoring antitumor T cell activity. Despite their broad clinical use, variability in treatment response and immune-related adverse events underscore the need for therapeutic optimization. This article provides an integrative overview of the pharmacokinetics (PKs) of anti-PD-1 antibodies—such as nivolumab, pembrolizumab, and cemiplimab—and examines pharmacokinetic–pharmacodynamic (PK-PD) relationships, highlighting the impact of clearance variability on drug exposure, efficacy, and safety. Baseline clearance and its reduction during therapy, together with interindividual variability, emerge as important dynamic biomarkers with potential applicability across different cancer types for guiding individualized dosing strategies. The review also discusses established biomarkers for anti-PD-1 therapies, including tumor PD-L1 expression and immune cell signatures, and their relevance for patient stratification. The evidence supports a shift from traditional weight-based dosing toward adaptive dosing and therapeutic drug monitoring (TDM), especially in long-term responders and cost-containment contexts. Notably, the inclusion of clearance-based biomarkers—such as baseline clearance and its reduction—into therapeutic models represents a key step toward individualized, dynamic immunotherapy. In conclusion, optimizing anti-PD-1 therapy through PK-PD insights and biomarker integration holds promise for improving outcomes and reducing toxicity. Future research should focus on validating PK-based approaches and developing robust algorithms (machine learning models incorporating clearance, tumor burden, and other validated biomarkers) for tailored cancer treatment. Full article
(This article belongs to the Special Issue Therapeutic Optimization of Anti-Tumor Drugs Based on Pharmacokinetics)
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21 pages, 555 KB  
Review
Beyond Visualization: Advanced Imaging, Theragnostics and Biomarker Integration in Urothelial Bladder Cancer
by Eduardo Albers Acosta, Lira Pelari Mici, Carlos Márquez Güemez, Clara Velasco Balanza, Manuel Saavedra Centeno, Marta Pérez Pérez, Guillermo Celada Luis, Cristina Quicios Dorado, José Daniel Subiela, Rodrigo España Navarro, Patricia Toquero Diez, Nuria Romero Laorden and Luis San José Manso
Cancers 2025, 17(19), 3261; https://doi.org/10.3390/cancers17193261 - 8 Oct 2025
Viewed by 373
Abstract
Background/Objectives: Bladder cancer is characterized by high recurrence and progression rates, posing a challenge to current diagnostic and treatment strategies. This review aims to provide a comprehensive overview of emerging technologies, including novel PET tracers, AI-assisted cystoscopy, theragnostics, and molecular biomarkers. Methods: [...] Read more.
Background/Objectives: Bladder cancer is characterized by high recurrence and progression rates, posing a challenge to current diagnostic and treatment strategies. This review aims to provide a comprehensive overview of emerging technologies, including novel PET tracers, AI-assisted cystoscopy, theragnostics, and molecular biomarkers. Methods: We performed a narrative review of the recent literature focusing on innovations in imaging, AI, theragnostics, and biomarker research relevant to bladder cancer diagnosis and management. Results: Several novel PET tracers, such as 68Ga-PSMA and fibroblast activation protein inhibitor (FAPI), demonstrated potential in improving detection sensitivity. AI-enhanced cystoscopy has shown promise in real-time lesion detection, while theragnostic agents enable combined diagnostic and therapeutic applications. Advances in molecular biomarkers, including circulating Tumor DNA (ctDNA) and gene expression signatures, offer new avenues for patient stratification and monitoring. Conclusions: Integration of advanced imaging, AI, theragnostics, and biomarker analysis may transform bladder cancer management, supporting personalized and more effective care strategies. Full article
(This article belongs to the Special Issue The Emerging Role of Multiplexed Imaging for Cancer Diagnosis and Therapy (2nd Edition))
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19 pages, 1056 KB  
Article
“Are You Just Looking to ‘Survive’?”: A Qualitative Study of Importance of Oncology Endpoints Beyond Overall Survival in Early-Stage Cancer
by Shelagh M. Szabo, Sarah Walker, Evelyn Griffin, Aya McMillan, Robert Bick, Frances Simbulan, Eon Ting and Stephanie Snow
Cancers 2025, 17(19), 3260; https://doi.org/10.3390/cancers17193260 - 8 Oct 2025
Viewed by 363
Abstract
Background/Objectives: In early-stage oncology clinical trials, the use of endpoints beyond overall survival (OS), including recurrence-free survival (RFS) or event-free survival (EFS), is becoming more common. To understand whether these outcomes are important to patients, this study explored the perceived value of non-OS [...] Read more.
Background/Objectives: In early-stage oncology clinical trials, the use of endpoints beyond overall survival (OS), including recurrence-free survival (RFS) or event-free survival (EFS), is becoming more common. To understand whether these outcomes are important to patients, this study explored the perceived value of non-OS endpoints among Canadians treated for early-stage cancer or with curative intent. Methods: Canadians treated for early-stage breast, lung, or gastrointestinal cancer participated in semi-structured interviews. Participants provided perspectives on OS, RFS, disease-free survival (DFS), EFS, and pathological complete response (pCR) endpoints. Reflexive thematic analysis was used to explore patterns in responses and alignment of trial endpoints with patient treatment goals, priorities and preferences. Results: The mean age of the 33 participants was 54.8 years, and 21 were female; 28 reported prior surgery, and 21 were also treated with chemotherapy (11 specified as neo-adjuvant; 9 specified adjuvant). All participants valued OS, and most viewed non-OS endpoints as reflective of their treatment priorities, including maintaining health-related quality of life and getting back to ‘normal’. They also valued timely and equitable treatment access and equated having access to new treatments with better options. While participants considered efficacy data from clinical trials provided by non-OS endpoints sufficient to want access to new treatments, the relative importance of being disease- or recurrence-free versus maximizing length of life differed according to recurrence status, prognosis, cancer type and life stage. Conclusions: These findings support the relevance and importance of non-OS endpoints to Canadians with early-stage cancer and highlight participants’ desire for rapid approval of treatments with demonstrated improvements in non-OS endpoints. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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36 pages, 916 KB  
Systematic Review
Failure to Rescue After Surgery for Pancreatic Cancer: A Systematic Review and Narrative Synthesis of Risk Factors and Safety Strategies
by Masashi Uramatsu, Yoshikazu Fujisawa, Paul Barach, Hiroaki Osakabe, Moe Matsumoto and Yuichi Nagakawa
Cancers 2025, 17(19), 3259; https://doi.org/10.3390/cancers17193259 - 8 Oct 2025
Viewed by 510
Abstract
Background: Failure to rescue (FTR), defined as death after major postoperative complications, is a critical quality indicator in pancreatic cancer surgery. Despite advances in surgical techniques and perioperative care, FTR rates remain high and vary across institutions. Methods: This systematic review [...] Read more.
Background: Failure to rescue (FTR), defined as death after major postoperative complications, is a critical quality indicator in pancreatic cancer surgery. Despite advances in surgical techniques and perioperative care, FTR rates remain high and vary across institutions. Methods: This systematic review uses a narrative synthesis followed by PRISMA 2020. A PubMed search (1992–2025) identified 83 studies; after screening, 52 studies (2010–2025) were included. Eligible designs were registry-based, multicenter, single-center, or prospective audits. Given substantial heterogeneity in study designs, FTR definitions, and outcome measures, a narrative synthesis was performed; no formal risk-of-bias assessment or meta-analysis was conducted. Results: Definitions of FTR varied (in-hospital, 30-day, 90-day, severity-based, and complication-specific cases). Reported rates differed by definition: average reported rates were 13.2% for 90-day CD ≥ III (G1); 10.3% for in-hospital/30-day CD ≥ III (G3); and 7.4% for 30-day “serious/major” morbidity (G8). Absolute differences were +3.0 and +2.9 percentage points (exploratory, descriptive comparisons). Five domains were consistently associated with lower FTR: (i) centralization to high-volume centers; (ii) safe adoption/refinement of surgical techniques; (iii) optimized perioperative management including early imaging and structured escalation pathways; (iv) patient-level risk stratification and prehabilitation; and (v) non-technical skills (NTSs) such as decision-making, situational awareness, communication, teamwork, and leadership. Among NTS domains, stress and fatigue management were not addressed in any included study. Limitations: Evidence is predominantly observational with substantial heterogeneity in study designs and FTR definitions; the search was limited to PubMed; and no formal risk-of-bias, publication-bias assessment, or meta-analysis was performed. Consequently, estimates and associations are descriptive/associative with limited certainty and generalizability. Conclusions: NTSs were rarely used or measured across the included studies, with validated instruments; quantitative assessment was uncommon, and no study evaluated stress or fatigue management. Reducing the FTR after pancreatic surgery will require standardized, pancreas-specific definitions of FTR, process-level rescue metrics, and deliberate strengthening of NTS. We recommend a pancreas-specific operational definition with an explicit numerator/denominator: numerator = all-cause mortality within 90 days of surgery; denominator = patients who experience major complications (Clavien–Dindo grade III–V, often labeled “CD ≥ 3”). Addressing the gaps in stress and fatigue management and embedding behavioral metrics into quality improvement programs are critical next steps to reduce preventable mortality after complex pancreatic cancer procedures. Full article
(This article belongs to the Special Issue Novel Diagnosis and Treatment Approaches in Pancreatic Cancer)
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32 pages, 1122 KB  
Review
Bispecific Monoclonal Antibodies in Diffuse Large B-Cell Lymphoma: Dawn of a New Era in Targeted Therapy
by Mattia Schipani, Matteo Bellia, Carola Sella, Riccardo Dondolin, Mariangela Greco, Abdurraouf Mokhtar Mahmoud, Clara Deambrogi, Riccardo Moia, Gianluca Gaidano and Riccardo Bruna
Cancers 2025, 17(19), 3258; https://doi.org/10.3390/cancers17193258 - 8 Oct 2025
Viewed by 813
Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL) worldwide. Currently, approximately sixty percent of patients are cured with R-CHOP as frontline treatment, while the remaining patients experience primary refractory or relapsed (R/R) disease. Recently, the introduction of Pola-R-CHP [...] Read more.
Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL) worldwide. Currently, approximately sixty percent of patients are cured with R-CHOP as frontline treatment, while the remaining patients experience primary refractory or relapsed (R/R) disease. Recently, the introduction of Pola-R-CHP as front-line therapy has represented a major advance in the management of DLBCL, resulting in improved outcomes. Prognosis of R/R DLBCL patients is poor, particularly for those eligible neither for chimeric antigen receptor (CAR) T-cell therapy nor autologous stem cell transplantation (ASCT), representing a significant unmet clinical need. The advent of bispecific monoclonal antibodies (BsAbs), such as bispecific T-cell engagers (BiTEs), dual affinity retargeting (DART) molecules and IgG-like bispecific antibodies, offers a novel promising therapeutic approach in the treatment of DLBCL, both as frontline treatment and in the R/R setting. BsAbs simultaneously engage two different antigens, a tumor-associated antigen and an immune cell antigen, redirecting T-cells against malignant cells and enhancing the immune response. Most BsAbs developed for the treatment of NHLs engage T-cells via CD3 and malignant B-cells via CD20, a surface antigen expressed on most lymphomatous cells. Engagement of malignant B-cells by BsAbs activates T-cells, leading to the release of multiple cytokines and potentially to two characteristic adverse events: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The most extensively studied BsAbs, in both the frontline and relapsed/refractory (R/R) settings, include epcoritamab, glofitamab, mosunetuzumab, and odronextamab. Epcoritamab and glofitamab have received FDA and EMA approval for R/R DLBCL after two or more systemic line of therapies. EMA has also approved glofitamab in combination with gemcitabine and oxaliplatin (GemOx) for patients with R/R DLBCL ineligible for ASCT, whereas this indication has not been approved by FDA. Odronextamab is approved by EMA for R/R DLBCL and FL in patients who have received at least two prior lines of therapy, but it has not been approved by FDA. Mosunetuzumab is approved by both agencies—but only for R/R follicular lymphoma (FL). BsAbs represent a breakthrough therapy in the treatment of DLBCL, especially in R/R diseases. The purpose of this article is to review the landscape of BsAbs in DLBCL. Full article
(This article belongs to the Special Issue Monoclonal Antibodies in Lymphoma)
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14 pages, 310 KB  
Article
Direct and Indirect Costs of Prostate Cancer: A Comprehensive Assessment of Economic and Social Impact
by Izabela Gąska, Aleksandra Czerw, Monika Pajewska, Olga Partyka, Andrzej Deptała, Anna Badowska-Kozakiewicz, Natalia Czerw, Dominika Mękal, Katarzyna Sygit, Katarzyna Wojtyła-Blicharska, Jarosław Drobnik, Piotr Pobrotyn, Dorota Waśko-Czopnik, Adam Wiatkowski, Michał Marczak, Tomasz Czapla, Ewa Bandurska, Weronika Ciećko, Elżbieta Grochans, Anna M. Cybulska, Daria Schneider-Matyka, Kamila Rachubińska and Remigiusz Kozlowskiadd Show full author list remove Hide full author list
Cancers 2025, 17(19), 3257; https://doi.org/10.3390/cancers17193257 - 8 Oct 2025
Viewed by 399
Abstract
Background: Prostate cancer is the second most common malignant cancer among men, and according to the predictions, the estimated number of new cases will substantially grow in the coming years. Therefore, the costs of the disease will increase as well. Methods: We conducted [...] Read more.
Background: Prostate cancer is the second most common malignant cancer among men, and according to the predictions, the estimated number of new cases will substantially grow in the coming years. Therefore, the costs of the disease will increase as well. Methods: We conducted a literature review of the state of knowledge about the costs of treatment and the economic burden of prostate cancer. The vast majority of studies were focused on direct costs only, which clearly shows the literature gap. Results: We focused on the estimates of direct costs, i.e., treatment of prostate cancer, adjuvant and neoadjuvant treatment, and supportive and palliative care, and indirect costs. Cost-effectiveness analyses indicated that docetaxel combined with androgen deprivation therapy (ADT) was the most cost-effective strategy for metastatic hormone-sensitive prostate cancer (incremental cost-effectiveness ratio (ICER): USD 13,647). In contrast, novel therapies such as PARP inhibitors and whole-genome-sequencing-guided treatments were not cost-effective unless drug prices were reduced by 47–70%. In the United States, 5-year cumulative treatment costs ranged from USD 48,000 for conservative management to over USD 91,000 for radiotherapy, while out-of-pocket expenses averaged AUD 1172 in Australia. Indirect costs were also considerable, with Slovakia reporting an increase in sick leave costs from EUR 1.2 million in 2014 to EUR 2.1 million in 2022. Conclusions: Metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer were the most frequent categories for various treatment cost evaluations. A few specific combinations of drugs were cost-effective only under the condition of dropping the unit prices of a medication. Further summarizing, reviewing, and developing a methodology for standardized comparisons are needed. Full article
(This article belongs to the Special Issue Cost-Effectiveness Studies in Cancers)
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19 pages, 693 KB  
Review
MYCN-Driven Metabolic Networks Are a Critical Dependency of High-Risk Neuroblastomas
by Michelle G. Pitts, Lindsay T. Bryant, Michael D. Buoncristiani and Eric J. Rellinger
Cancers 2025, 17(19), 3256; https://doi.org/10.3390/cancers17193256 - 8 Oct 2025
Viewed by 370
Abstract
Neuroblastoma is a devastating pediatric solid tumor that, despite significant recent advances, still accounts for nearly 15% of all childhood cancer deaths. Patients are risk stratified based on a number of features, including amplification of the MYCN oncogene, yet targeting MYCN itself has [...] Read more.
Neuroblastoma is a devastating pediatric solid tumor that, despite significant recent advances, still accounts for nearly 15% of all childhood cancer deaths. Patients are risk stratified based on a number of features, including amplification of the MYCN oncogene, yet targeting MYCN itself has been unsuccessful to date. The complex interplay between this oncogene and its many metabolic targets has proven challenging and is only beginning to be understood in the context of pediatric tumors. It is increasingly recognized, however, that MYCN-driven metabolic rewiring and concomitant increases in biosynthetic precursors has the potential to drive many aspects of tumor development. Furthermore, emerging research suggests that improving overall therapeutic outcomes for neuroblastoma patients may well require individual metabolic profiling, allowing personalized simultaneous targeting of multiple metabolic nodes. In this review, we outline clinically relevant research involving MYCN-driven metabolic derangements, including increased glucose uptake, polyamine synthesis, glycosylation, and others, and attempt to summarize the influence of MYCN on important metabolic genes and druggable protein targets. We spotlight emerging research in glycosylation and its modulation as an often overlooked but increasingly promising therapeutic area. It is our hope that this document will provide utility for both clinicians and scientists seeking to understand how the MYCN oncogene and metabolism are critically intertwined. Full article
(This article belongs to the Special Issue Neuroblastoma: Molecular Insights and Clinical Implications)
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20 pages, 1386 KB  
Article
AI-Assistance Body Composition CT at T12 and T4 in Lung Cancer: Diagnosing Sarcopenia, and Its Correlation with Morphofunctional Assessment Techniques
by Maria Zhao Montero-Benitez, Alba Carmona-Llanos, Rocio Fernández-Jiménez, Alicia Román-Jobacho, Jaime Gómez-Millán, Javier Modamio-Molina, Eva Cabrera-Cesar, Isabel Vegas-Aguilar, Maria del Mar Amaya-Campos, Francisco J. Tinahones, Esther Molina-Montes, Manuel Cayón-Blanco and Jose Manuel García-Almeida
Cancers 2025, 17(19), 3255; https://doi.org/10.3390/cancers17193255 - 8 Oct 2025
Viewed by 292
Abstract
Background: Sarcopenia and low muscle mass are prevalent and prognostically relevant in patients with lung cancer, yet their diagnosis remains challenging in routine clinical practice. Opportunistic assessment using computed tomography (CT) has emerged as a valuable tool for body composition evaluation. We aimed [...] Read more.
Background: Sarcopenia and low muscle mass are prevalent and prognostically relevant in patients with lung cancer, yet their diagnosis remains challenging in routine clinical practice. Opportunistic assessment using computed tomography (CT) has emerged as a valuable tool for body composition evaluation. We aimed to assess the utility of thoracic CT at T12 and T4 levels in identifying sarcopenia and low muscle mass and explore their correlation with morphofunctional tools such as bioelectrical impedance vector analysis (BIVA), nutritional ultrasound (NU), and functional performance tests. Methods: In this prospective observational study, 80 patients with lung cancer were evaluated at diagnosis. Body composition was assessed using BIVA-, NU-, and CT-derived parameters at T12 and T4 levels. Functional status was measured using the Timed Up and Go (TUG) and 30-Second Chair Stand Test. Sarcopenia was defined according to EWGSOP2 criteria. Results: Sarcopenia was identified in 20% of patients. CT-derived indices at T12CT demonstrated better diagnostic performance than T4CT. For detecting low muscle mass, the optimal SMI cut-off values were SMI_T12CT < 31.98 cm2/m2 and SMI_T4CT < 59.05 cm2/m2 in men and SMI_T12CT < 28.23 cm2/m2 and SMI_T4CT < 41.69 cm2/m2 in women. For sarcopenia diagnosis, the values were SMI_T12CT < 24.78 cm2/m2 and SMI_T4CT < 57.23 cm2/m2 in men and SMI_T12CT < 21.24 cm2/m2 and SMI_T4CT < 49.35 cm2/m2 in women. A combined model including SMI_T12CT, RF_CSA, and the 30 s squat test showed high diagnostic accuracy (AUC = 0.826). In multivariable analysis, lower SMA_T12CT was independently associated with risk of sarcopenia (OR = 0.96, 95% CI: 0.92–0.99, p = 0.022), as were older age (OR = 1.23, 95% CI: 1.07–1.47, p = 0.010) and fewer repetitions in the 30 s squat test (OR = 0.78, 95% CI: 0.63–0.91, p = 0.007). Conclusions: CT-derived body composition assessment, particularly at the T12 level, shows good correlation with morphofunctional tools and may offer a reliable and timely alternative for identifying sarcopenia and low muscle mass in patients with lung cancer. Full article
(This article belongs to the Special Issue CT/MRI/PET in Cancer)
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15 pages, 452 KB  
Review
The Impact of Social Determinants of Health on Supportive and Palliative Care in Pancreatic Cancer Management: A Narrative Review
by Sterre van Herwijnen, Vishnu Jayaprakash, Camila Hidalgo Salinas, Joseph R. Habib, Daniel Brock Hewitt, Greg D. Sacks, Christopher L. Wolfgang, Katherine A. Morgan, Brian J. Kaplan, Michael D. Kluger, Alok Aggarwal and Ammar A. Javed
Cancers 2025, 17(19), 3254; https://doi.org/10.3390/cancers17193254 - 8 Oct 2025
Viewed by 376
Abstract
Background: Pancreatic cancer is a challenging malignancy with an aggressive biology and limited treatment options, contributing to low survival rates. Supportive and palliative care play a key role in improving the quality of life and psychological distress for patients and their families. However, [...] Read more.
Background: Pancreatic cancer is a challenging malignancy with an aggressive biology and limited treatment options, contributing to low survival rates. Supportive and palliative care play a key role in improving the quality of life and psychological distress for patients and their families. However, appropriate delivery and effectiveness of these interventions may be influenced by social determinants of health (SDOH). These factors create significant barriers for patients, influencing their access to care and ability to make informed decisions. This review explores the role of SDOH in supportive and palliative care of pancreatic cancer patients and identifies areas for improvement to enhance this type of care for vulnerable populations. Methods: A thorough narrative review was carried out to evaluate the influence of social determinants of health on supportive and palliative care in the management of pancreatic cancer, focusing on symptom management, psychosocial support, nutritional support, advance care planning, rehabilitation, functional support, and care coordination. Results: This review demonstrates that disparities exist. Black and Asian patients receive less pain medications; those with lower level of education struggle to access psychological support; Hispanic and Black patients often do not receive needed nutritional care; and end-of-life planning is less common among non-White and less-educated patients. Conclusions: SDOH significantly affects the experience and delivery of supportive and palliative care in pancreatic cancer patients, exacerbating inequities across multiple domains of care. Addressing these disparities requires coordinated efforts at clinical, organizational, and policy levels to ensure equitable access to care for all patients in their final phase of life. Integrating attention to SODH into care delivery models can improve outcomes and enhance quality of life for these patients. Full article
(This article belongs to the Special Issue Impact of Social Determinants on Cancer Care)
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28 pages, 5673 KB  
Article
Liver-Specific Nanoparticle-Mediated Delivery and MMP-Triggered Release of Veratridine to Effectively Target Metastatic Colorectal Cancer
by Mahadi Hasan, Morgan Eikanger, Sanam Sane, Krishantha S. K. Wijewardhane, John L. Slunecka, Jessica Freeling, Khosrow Rezvani and Grigoriy Sereda
Cancers 2025, 17(19), 3253; https://doi.org/10.3390/cancers17193253 - 8 Oct 2025
Viewed by 469
Abstract
Background: Despite considerable advances to improve colorectal cancer (CRC) survival over the last decade, therapeutic challenges remain due to the rapid metastatic dissemination of primary tumors. This study revealed the apoptotic and anti-growth mechanism of VTD, a previously used anti-hypertensive supplement, can elevate [...] Read more.
Background: Despite considerable advances to improve colorectal cancer (CRC) survival over the last decade, therapeutic challenges remain due to the rapid metastatic dissemination of primary tumors. This study revealed the apoptotic and anti-growth mechanism of VTD, a previously used anti-hypertensive supplement, can elevate UBXN2A, a known tumor suppressor protein in CRC, and simultaneously enhance intrinsic and extrinsic apoptosis in metastatic cancer cells. Methods and Results: An AOM/DSS mouse model of CRC showed that UBXN2A haplosufficient (UBXN2A +/−) mice treated with VTD had less tumor burden than mice with the full UBXN2A gene treated with vehicle. We have previously shown that casein-coated mesoporous silica nanoparticles (MSNs) offer an effective local delivery of drugs at tumor sites. Our findings demonstrate that the high rate of extracellular release of matrix metalloproteinases (MMPs), particularly MMP-7, by metastatic colon cancer cells, triggers the release of VTD from casein-coated mesoporous MSNs. This shows the “Zip Code” mechanism for the local enrichment of VTD at the tumor sites. After in vitro drug release verification, two independent mouse experiments, a xenograft and a splenolepatic metastatic mouse model of CRC, were used to evaluate the therapeutic efficacy of VTD-loaded and casein-coated carboxylated mesoporous silica nanoparticles, MSN-COOH/VTD/CAS (VTD, 0.2 mg/kg). Animal experiments revealed that MSN-COOH/VTD/CAS (VTD, 0.2 mg/kg) slows down the progress of tumors. Mass spectrometry (MS) revealed improved pharmacokinetics (PK) profile as MSN-COOH/VTD/CAS had less VTD accumulation in non-cancerous organs compared to pure VTD. We further improved nanoparticle targeting and drug release by shifting to calcium-based particles (CBPs). The engineered CBPs demonstrated higher drug-releasing performance. Without the MMPs trigger, MSNs show slow and continuous “drug leak” over longer period of time whereas CCSMPs stops leakage within an hour. Additionally, CBPs showed higher sensitivity to MMP-7 than MMP-9, enhancing the targetability of CBPs for CRC metastatic tumors with excessive extracellular MMP-7. Conclusions: This study introduces a new platform utilizing nanoparticle-based site-specific delivery of a plant-based anti-metastatic molecule, veratridine, with enhanced safety and therapeutic efficacy for the treatment of metastatic CRC. Full article
(This article belongs to the Special Issue Novel Approaches to the Management of Patients with Gastrointestinal Tumors)
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11 pages, 433 KB  
Article
Comprehensive Evaluation of Hepatotoxicity Following Radiation Therapy in Breast Cancer Patients
by Jun Yeong Song, Soon Woo Hong, Sang-Won Kang, Bum-Sup Jang and In Ah Kim
Cancers 2025, 17(19), 3252; https://doi.org/10.3390/cancers17193252 - 8 Oct 2025
Viewed by 319
Abstract
Purpose: The liver is susceptible to adverse effects from radiation therapy (RT) and systemic therapy (ST) for breast cancer, given its anatomical proximity. Thus, we evaluated hepatotoxicity after RT and ST for breast cancer. Methods: This multicenter retrospective study included breast cancer patients [...] Read more.
Purpose: The liver is susceptible to adverse effects from radiation therapy (RT) and systemic therapy (ST) for breast cancer, given its anatomical proximity. Thus, we evaluated hepatotoxicity after RT and ST for breast cancer. Methods: This multicenter retrospective study included breast cancer patients treated with RT in 2021 and underwent a liver function test (LFT) before and after RT. Patients with bilateral breast cancer or a history of thoracic or abdominal RT and liver disease were excluded. Changes in Common Terminology Criteria for Adverse Events (CTCAE) grading of liver enzyme elevation (LEE) of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and its associations with Dose-volume histogram (DVH) parameters and other clinical factors were analyzed. Results: In total, 529 patients were included in the analysis. Median values of mean liver dose, V5Gy, V10Gy, and V20Gy dose to the liver were 1.37 Gy, 4.3%, 2.1%, and 0.9%, respectively. In the post-RT LFT, 6 (1.1%), 9 (1.7%), and 25 (4.7%) patients showed CTCAE grade elevation of AST, ALT and ALP, respectively, with most cases being grade 1. Three patients (0.6%) met the diagnostic criteria for radiation-induced liver disease (RILD). In multivariate logistic regressions including various DVH parameters, neoadjuvant therapy was associated with LEE. Conclusions: The incidences of LEE and RILD after multimodal therapy for breast cancer were limited, suggesting that RT and ST can be considered safe in terms of hepatotoxicity. Nevertheless, caution in treating patients who underwent neoadjuvant therapy, especially to those with underlying liver disease, might help minimize LEE. Full article
(This article belongs to the Section Clinical Research of Cancer)
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25 pages, 3673 KB  
Review
Recent Advances in Ablative Therapies for Hepatocellular Carcinoma
by Saad Abu Zahra, Arsalan Nadeem, Ashima Kundu, Nick Gibson, Ali Haggaz, Kent T. Sato, Robert J. Lewandowski and Andrew C. Gordon
Cancers 2025, 17(19), 3251; https://doi.org/10.3390/cancers17193251 - 7 Oct 2025
Viewed by 642
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with curative surgical interventions feasible for a minority of patients. This review highlights recent advances in thermal (e.g., radiofrequency ablation, microwave ablation, and cryoablation) and nonthermal (e.g., ethanol ablation and irreversible electroporation) [...] Read more.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with curative surgical interventions feasible for a minority of patients. This review highlights recent advances in thermal (e.g., radiofrequency ablation, microwave ablation, and cryoablation) and nonthermal (e.g., ethanol ablation and irreversible electroporation) ablative modalities as curative-intent alternatives to surgery. Evolving applications of transcatheter intra-arterial radioembolization (TARE) with ablative dosimetry will be explored, and histotripsy, an emerging technology, will be introduced. Full article
(This article belongs to the Section Methods and Technologies Development)
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21 pages, 6412 KB  
Review
Eosinophil ETosis and Cancer: Ultrastructural Evidence and Oncological Implications
by Rosario Caruso, Valerio Caruso and Luciana Rigoli
Cancers 2025, 17(19), 3250; https://doi.org/10.3390/cancers17193250 - 7 Oct 2025
Viewed by 301
Abstract
Eosinophils are innate immune cells that infiltrate tissues in response to cell proliferation and necrosis, which occurs during normal injury repair, parasitic infections, allergies, and cancer. Their involvement in cancer is controversial particularly with regard to tumor-associated tissue eosinophilia (TATE) and a recently [...] Read more.
Eosinophils are innate immune cells that infiltrate tissues in response to cell proliferation and necrosis, which occurs during normal injury repair, parasitic infections, allergies, and cancer. Their involvement in cancer is controversial particularly with regard to tumor-associated tissue eosinophilia (TATE) and a recently defined mechanism of extracellular trap cell death (ETosis), a particular type of eosinophil cell death that is distinct from both apoptosis and necrosis. This narrative review synthesizes the literature regarding the prognostic significance of TATE, focusing on eosinophil ETosis and the important role of transmission electron microscopy (TEM) in its detection and morphological characterization. The prognostic role of TATE is contradictory: in certain tumors, it is a favorable prognostic marker, while in others, it is unfavorable. However, recent research reveals that TATE is associated with a better prognosis in non-viral neoplasms, but it may correlate with a poor prognosis in virus-related neoplasms, such as human T-lymphotropic virus type 1 (HTLV-1)-associated lymphomas and HPV-positive carcinomas. Our ultrastructural investigations revealed distinct phases of eosinophil ETosis in gastric cancer, which were defined by chromatin decondensation, plasma membrane disruption, granule discharge, and development of extracellular traps. We observed synapse-like interactions between eosinophils, exhibiting ETosis or compound exocytosis, and tumor cells, which showed various degrees of cellular damage, ultimately leading to colloid-osmotic tumor cell death. TEM provides important insights into eosinophil-mediated cytotoxicity, requiring further investigation as potential immune effector mechanisms in non-viral tumors. TATE evaluation, together with the viral status of the neoplasia, may be useful to confirm its prognostic significance and consequently its therapeutic implication in specific cancers. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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11 pages, 581 KB  
Article
Diagnostic and Therapeutic Management of Mesothelioma of the Tunica Vaginalis Testis: A Population-Based Study in Italy
by Giovanni Luca Ceresoli, Simona Stella, Barbara Dallari, Riccardo Perduri, Cinzia Storchi, Luigi Vimercati, Sara Piro, Lucia Giovannetti, Ugo Fedeli, Veronica Casotto, Enrica Migliore, Antonella Stura, Carlo Genova, Lucia Benfatto, Francesca Larese Filon, Flavia D’Agostin, Ilaria Cozzi, Italo Francesco Angelillo, Eugenia Spata, Stefano Murano, Iolanda Grappasonni, Cristiana Pascucci, Massimo Melis, Fabrizio Stracci, Alessandro Marinaccio, Alessandra Binazzi, Dario Consonni and Carolina Mensiadd Show full author list remove Hide full author list
Cancers 2025, 17(19), 3249; https://doi.org/10.3390/cancers17193249 - 7 Oct 2025
Viewed by 312
Abstract
Background: Mesothelioma of the tunica vaginalis testis (MTVT) is an exceedingly rare tumor. We performed a registry-based study on MTVT patient management and survival in Italy. Methods: Cases were extracted from the dataset of the Italian National Mesothelioma Registry. A descriptive analysis of [...] Read more.
Background: Mesothelioma of the tunica vaginalis testis (MTVT) is an exceedingly rare tumor. We performed a registry-based study on MTVT patient management and survival in Italy. Methods: Cases were extracted from the dataset of the Italian National Mesothelioma Registry. A descriptive analysis of patient characteristics, including asbestos exposure, clinical presentation, diagnostic work-up and therapeutic management, was performed. Overall survival was evaluated. We calculated hazard ratios (HR) and 95% confidence intervals (CI) for selected variables by fitting univariate and multivariable Cox models. Results: Overall, 104 patients with MTVT were included. Median age was 72 years (range 17–92). Epithelioid histotype was the most frequent. Previous asbestos exposure was identified in two thirds of cases. Data on diagnostic and therapeutic management were available for 74 patients (71%). The most frequent presentations were scrotal swelling/mass, hydrocele and inguinal pain. All patients underwent surgery, mostly with orchi-funicolectomy. Adjuvant therapy was administered to 15 patients (20%). Overall median survival was 26.2 months (95% CI 22.1–52.1); 3-, 5- and 10-year survival was 49%, 30% and 18%. Older age at diagnosis and presence of distant metastasis (HR 1.91, CI: 0.85–4.26) were negative prognostic factors. Adjuvant therapy was associated with higher mortality (HR 2.54, CI: 1.25–5.15), indicating a more advanced stage at diagnosis. Conclusions: Surgery remains the mainstay of treatment for MTVT; adjuvant therapy in our study did not improve outcome. Data from cancer registries are essential for rare cancers, but they should be integrated routinely with additional diagnostic and therapeutic information. Full article
(This article belongs to the Section Cancer Informatics and Big Data)
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25 pages, 1363 KB  
Review
Guardians in the Gut: Mechanistic Insights into a Hidden Ally Against Triple-Negative Breast Cancer
by Kayla Jaye, Muhammad A. Alsherbiny, Dennis Chang, Chun-Guang Li and Deep Jyoti Bhuyan
Cancers 2025, 17(19), 3248; https://doi.org/10.3390/cancers17193248 - 7 Oct 2025
Viewed by 380
Abstract
The gut microbiome possesses a diverse range of biological properties that play a role in maintaining host health and preventing disease. Gut microbial metabolites, including short-chain fatty acids, natural purine nucleosides, ellagic acid derivatives, and tryptophan metabolites, have been observed to have complex [...] Read more.
The gut microbiome possesses a diverse range of biological properties that play a role in maintaining host health and preventing disease. Gut microbial metabolites, including short-chain fatty acids, natural purine nucleosides, ellagic acid derivatives, and tryptophan metabolites, have been observed to have complex and multifaceted roles in the gut and in wider body systems in the management of disease, including cancer. Triple-negative breast cancer is the most aggressive subtype of breast cancer, with restricted treatment options and poor prognoses. Recently, preclinical research has investigated the antiproliferative potential of gut microbial metabolites against this type of breast cancer with promising results. However, little is understood about the mechanisms of action and molecular pathways driving this antiproliferative potential. Understanding the complex mechanisms of action of gut microbial metabolites on triple-negative breast cancer will be instrumental in the investigation of the combined administration with standard chemotherapeutic drugs. To date, there is a paucity of research studies investigating the potential synergistic interactions between gut microbial metabolites and standard chemotherapeutic drugs. The identification of synergistic potential between these compounds may provide alternate and more effective therapeutic options in the treatment and management of triple-negative breast cancer. Further investigation into the mechanistic action of gut microbial metabolites against this breast cancer subtype may support the administration of more cost-effective treatment options for breast cancer, with an aim to reduce side effects associated with standard treatments. Additionally, future research will aim to identify more potent metabolite–drug combinations in the mitigation of triple-negative breast cancer progression and metastasis. Full article
(This article belongs to the Special Issue Gut Microbiome, Diet and Cancer Risk)
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