Cancer Medicine最新文献

{"title":"Can Multiparametric Digital Whole-Slide Image Analysis Improve Recurrence Risk Stratification in Oral Tongue Squamous Cell Carcinoma?","authors":"Tatjana Heusinger,&nbsp;Tamás Dániel Csűry,&nbsp;Anna Zsófia Csűry,&nbsp;Hamed Mirbagheri,&nbsp;Marion Dörrich,&nbsp;Andreas M. Kist,&nbsp;Philipp Grundtner,&nbsp;Sandra Beyer,&nbsp;Markus Eckstein,&nbsp;Antoniu-Oreste Gostian","doi":"10.1002/cam4.72401","DOIUrl":"10.1002/cam4.72401","url":null,"abstract":"<p>Recurrence in oral tongue squamous cell carcinoma (TSCC) remains a prognostic challenge, which necessitates additional prognostic approaches reflecting tumor biology. Therefore, we developed an objective, observer-independent, multiparametric model incorporating features of the tumoral and stromal compartments. Digitized whole-slide images from 80 patients with TSCC were analyzed using a combination of semi-automatic and deep learning-based approaches. We extracted quantitative histomorphological features, including tumor/stroma ratio (TSR), lymphocyte/stromal cell ratio in the tumor stroma (LSCR), and the modified Polsby-Popper (MPP) score reflecting tumor disjointedness. Human trophoblast cell surface glycoprotein (Trop-2) expression was assessed by immunohistochemistry in central and invasive-front tumor regions sampled via tissue microarrays (TMA) and quantified using the H-score. A composite score (CS) was constructed by summing points from these parameters; as Trop-2 did not improve cross-validated discrimination, a final three-marker CS (TSR, LSCR, MPP) was adopted as the final model. Patients were stratified into prognostic groups and recurrence-free survival (RFS) was analyzed. While individual parameters showed only trends, the CS stratified patients into poor, intermediate and favorable prognosis groups with 5-year RFS probabilities of 64.6%, 75.3%, and 100.0%. Repeated five-fold cross-validation yielded a cross-fitted consensus concordance index of 0.587 (mean per-repetition concordance index 0.567 ± 0.039), compared with an apparent concordance index of 0.676, with no evidence of a difference from conventional prognostic factors. In exploratory multivariable Firth-penalized Cox regression adjusted for pT3–pT4a category, the favorable group showed a lower recurrence hazard than the poor group (HR 0.104, 95% CI 0.001–0.854, <i>p</i> = 0.0316); this non-cross-validated estimate is fragile given the small favorable group without recurrence events. This observer-independent whole-slide image approach may provide complementary prognostic information to conventional histological features but requires external validation.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.72401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149339988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opportunities and Challenges in FLASH Radiotherapy: Focusing on Normal Tissue Protection Effects and Clinical Translation Bottleneck","authors":"Xuan-Lu He,&nbsp;Hong-Shuai Li,&nbsp;Fei Tang,&nbsp;Yi Zhang,&nbsp;Wen Yang,&nbsp;Ya-Ting Lu,&nbsp;Jia-Min Guo,&nbsp;Wen-Jun Meng,&nbsp;Zhen Liu,&nbsp;Yu Zhang,&nbsp;Xing-Chen Peng","doi":"10.1002/cam4.72392","DOIUrl":"10.1002/cam4.72392","url":null,"abstract":"<p>FLASH radiotherapy (FLASH-RT) has garnered significant attention for its “FLASH effect”, which selectively protects normal tissues while maintaining tumor-killing efficacy at ultra-high dose rates (UHDR). This technology represents a promising but still investigational therapeutic strategy in radiation oncology. Since the initial confirmation of the FLASH effect in mouse experiments in 2014, related research has rapidly advanced in key radiation physics parameters, radiation types, and biological mechanisms. However, a lack of consensus on its critical triggering conditions, tissue-specific thresholds, and standardized parameters has hindered its transition from laboratory to clinical application. This review systematically outlines the physical triggering conditions of the FLASH effect, revealing its dependence on a multidimensional combination of parameters including dose rate, single-fraction dose, pulse time structure, and radiation type. It also delves into the underlying multiscale biological mechanisms, encompassing radiochemical aspects such as transient oxygen depletion and free radical kinetics, cellular processes including DNA damage repair and cell death patterns, and systemic changes like immune microenvironment remodeling. It further examines three core challenges hindering FLASH-RT's clinical implementation: technical feasibility and equipment limitations, the complexity and uncertainty of biological mechanisms, and challenges in clinical practice and standardization. This review aims to dissect current research progress and critical issues, providing guidance for advancing FLASH-RT's clinical application.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.72392","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Validation of the MAGIC-D Index in Unresectable Biliary Tract Cancer Treated With Durvalumab Plus Chemotherapy","authors":"Tianao Zhan,&nbsp;Hongwei Huang,&nbsp;Juncheng Zhan,&nbsp;Feng Xia,&nbsp;Tianyin Shao,&nbsp;Xinkang Liu,&nbsp;Jun Shen,&nbsp;Xingbin Xu,&nbsp;Yawei Fan,&nbsp;Qi Cheng","doi":"10.1002/cam4.72254","DOIUrl":"10.1002/cam4.72254","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The MAGIC-D index was originally developed to predict outcomes in advanced biliary tract cancer (BTC) patients receiving durvalumab-gemcitabine-cisplatin (Durva-Gem-Cis). This study aimed to assess the efficacy and safety of various durvalumab-chemotherapy regimens for unresectable BTC patients and the broader applicability of the MAGIC-D index.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study retrospectively recruited unresectable BTC patients receiving durvalumab-chemotherapy from 2021 to 2024. Overall survival (OS) and progression-free survival (PFS) were assessed, and patients were risk-stratified using the MAGIC-D index.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 89 patients were included in the analysis. Between the Durva-Gem-Cis group and the durvalumab plus other chemotherapy regimens (Durva-Other Regimens) group, the median OS (12.9 vs. 13.9 months) and PFS (5.5 vs. 6.2 months) were comparable. Patients were risk-stratified into three risk groups (median OS: 21.0, 12.9, 12.4 months for the low-, intermediate-, and high-risk groups, respectively; <i>p</i> = 0.002) using the MAGIC-D index, which achieved a concordance index (C-index) of 0.637. The Cox regression analysis showed serum CA 19-9 level, high Ki67 expression and the MAGIC-D index were related to OS. An exploratory model named the modified MAGIC-D index, incorporating Ki67 and CA 19-9 into the MAGIC-D index, showed promising discrimination of survival among risk groups (25.0 vs. 12.9 vs. 9.1 months, <i>p</i> &lt; 0.001) with a C-index of 0.709.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Durvalumab plus different chemotherapy regimens achieves comparable outcomes in the treatment of unresectable BTC. Incorporating Ki67 and CA 19-9 into the MAGIC-D index may enhance risk stratification, but external validation in larger independent cohorts is required before clinical application.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13732815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Associated With Recurrence After Adjuvant Gemcitabine and Nab-Paclitaxel in Patients With Resected Pancreatic Ductal Adenocarcinoma.","authors":"Tao Xia, Chi Cheng, Yudi Meng, Hao Huang, Duo Li, Renfan Zhu, Chengcong Qiu, Yongfei Hua","doi":"10.1002/cam4.72491","DOIUrl":"10.1002/cam4.72491","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis despite curative-intent resection and adjuvant therapy. Gemcitabine plus nab-paclitaxel (Gem-NAP) has become a standard adjuvant regimen for PDAC, yet recurrence rates remain high. This study aimed to identify clinical and pathological factors associated with recurrence and survival in patients receiving adjuvant Gem-NAP following PDAC resection.</p><p><strong>Methods: </strong>We retrospectively identified 210 patients with resected PDAC who received adjuvant gemcitabine and nab-paclitaxel at a single institution between May 2017 and October 2024. Clinicopathological characteristics, recurrence patterns, disease-free survival (DFS), and overall survival (OS) were analyzed. Univariate and multivariate models were utilized to identify independent predictors of recurrence and survival.</p><p><strong>Results: </strong>In total, 132 patients (62.9%) experienced recurrence, with a median DFS of 21.0 months (95% CI: 16.7-25.3) and a median OS of 39.0 months (95% CI: 32.7-45.3). Local recurrence (28.6%) and liver metastasis (24.8%) were the most common recurrence sites. Multivariable analysis revealed that preoperative CA19-9 > 37 U/mL (OR: 2.28; 95% CI: 1.19-4.34; p = 0.01) and a lymph node ratio (LNR) > 0.14 (OR: 2.98; 95% CI: 1.19-7.47; p = 0.02) were significantly associated with recurrence. Independent predictors of worse DFS included elevated preoperative CA19-9 (> 37 U/mL) (HR: 1.59; 95% CI: 1.04-2.43; p = 0.03), LNR > 0.14 (HR: 1.88; 95% CI: 1.23-2.89; p < 0.01), R1 resection (HR: 2.71; 95% CI: 1.36-5.38; p < 0.01), and lymphovascular invasion (LVI) (HR: 1.59; 95% CI: 1.09-2.30; p = 0.02). For OS, the independent predictors were R1 resection (HR: 3.00; 95% CI: 1.45-6.22; p < 0.01), LVI positivity (HR: 1.55; 95% CI: 1.03-2.34; p = 0.04), and LNR > 0.14 (HR: 1.76; 95% CI: 1.11-2.80; p = 0.02).</p><p><strong>Conclusions: </strong>Recurrence after adjuvant gemcitabine and nab-paclitaxel in patients with resected pancreatic cancer remains common. A high lymph node ratio, R1 resection, and lymphovascular invasion were powerful independent predictors of both poor DFS and OS.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13735890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality Indicators in End-of-Life Care for Children With Cancer in Low- and Middle-Income Countries.","authors":"Michael J McNeil, Ximena Garcia Quintero, Marta Salek, Asya Agulnik, Julia Downing, Veronica Dussel, Paola Friedrich, Wendy Gomez Garcia, Emily E Johnston, Narine Movsisyan, Eve Namisango, Krithika Rao, Ursula M Sansom-Daly, Kimberley Widger, Lori Wiener, Carlos Rodriguez-Galindo, Justin N Baker","doi":"10.1002/cam4.72443","DOIUrl":"10.1002/cam4.72443","url":null,"abstract":"<p><strong>Background: </strong>Around 90% of children with cancer live in low- and middle-income countries (LMICs), with the majority dying of their disease. Despite the need for quality end-of-life (EoL) care in LMICs, access and integration remain limited. Quality indicators (QIs) can assess and provide standards for high-quality care. The aim of this study was to develop QIs for EoL care for children diagnosed with cancer in LMICs.</p><p><strong>Methods: </strong>The QIs were identified and prioritized through a multi-phase process: (1) literature review identified potential QIs from existing guidelines, standards, and published studies; (2) modified Delphi approach engaged global experts to assess the importance and feasibility of QIs; and (3) prioritization conducted using a Discrete Choice Experiment (DCE) with experts and dot voting prioritization exercise with bereaved family members.</p><p><strong>Results: </strong>From the literature review, 73 potential QIs were identified. Fifty-six global experts from 27 countries participated in the modified Delphi. Sixty-four indicators across seven domains were deemed important with 25 identified as both important and feasible. Forty-one global experts from 23 countries participated in the DCE prioritization and 12 bereaved family members from nine countries participated in the dot voting prioritization. While experts and family members prioritized some indicators similarly (i.e., symptom management), family members placed higher priority on QIs addressing communication and anticipatory guidance.</p><p><strong>Conclusion: </strong>This study describes a robust, context-specific process which identified QIs for pediatric EoL care in LMICs. Future efforts will pilot and refine the QIs to demonstrate feasibility, sustainability, and impact on care quality.</p><p><strong>Precis: </strong>This study assessed potential quality indicators (QIs) for pediatric end-of-life (EoL) care in low- and middle-income countries (LMICs) through a multi-phase process involving global experts and bereaved families. The findings provide a set of potential QIs to evaluate and improve EoL care for children with cancer in LMICs.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13720528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Healthcare Utilization and Differential Outcomes for Pediatric Cancer Versus Non-Cancer Patients.","authors":"Yujie Chen, Martin Yi, Catherine C Aftandilian, Melissa P Beauchemin, Christine Cunningham, Emily Larimer, Jennifer Oberg, Benjamin L May, Keith Morse, Karthik Natarajan, David Noyd, Vicki Soucek, Rhea K Khurana, Phil Sim, Lin Lawrence Guo, Lillian Sung","doi":"10.1002/cam4.72459","DOIUrl":"10.1002/cam4.72459","url":null,"abstract":"<p><strong>Background: </strong>The Observational Medical Outcomes Partnership Common Data Model (OMOP CDM) is a data standard that enables multicenter research. Primary objective was to describe the magnitude of healthcare utilization in pediatric cancer versus non-cancer patients. Secondary objective was to compare 6-month clinical outcomes related to abnormal lab tests and mortality.</p><p><strong>Methods: </strong>In this multicenter retrospective study, we included pediatric patients 0-18 years at first medication administration. Cancer patients had a malignant neoplastic disease diagnosis and received chemotherapy. Index date was the first chemotherapy date. Non-cancer patients were assigned analogous index dates based on randomly sampled first medication to chemotherapy intervals. Outcomes were measured within 6 months of index date. Healthcare utilization included encounters, procedures, radiology, lab tests, and medications.</p><p><strong>Results: </strong>Among 2810 cancer and 11,240 non-cancer patients, all evaluated healthcare utilization measures were significantly more common in cancer patients. The largest relative differences were observed for long inpatient stay (risk ratio [RR] 26.32, 95% confidence interval [CI] 15.00-46.17), computed tomography (RR 23.59, 95% CI 19.24-28.92), blood culture (RR 37.04, 95% CI 9.58-143.14), and intravenous medication (RR 17.69, 95% CI 8.75-35.75). Death within 6 months was higher for cancer versus non-cancer patients (RR 38.37, 95% CI 12.91-114.04).</p><p><strong>Conclusions: </strong>Using the OMOP CDM, we found greater healthcare utilization and worse clinical outcomes among pediatric cancer patients than non-cancer patients, with the largest relative differences observed for inpatient stay, computed tomography, blood culture, and intravenous medication. These findings provide insight into resource utilization patterns and illustrate the OMOP CDM research potential for multicenter studies.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13720334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age, Comorbidity Burden and Treatment Outcomes in Mature B-Cell Lymphoproliferative Disorders: A Real-World Study.","authors":"Kevin Nasrinfar, Harrison Wildhaber, Rudolf Rohr, Gaëlle Rhyner Agocs, Urban Novak, Alessandra Curioni-Fontecedro, Vérène Dougoud-Chauvin","doi":"10.1002/cam4.72460","DOIUrl":"10.1002/cam4.72460","url":null,"abstract":"<p><strong>Introduction: </strong>Treatment decisions in older patients with mature B-cell lymphoproliferative disorders (MBLD) are frequently guided by chronological age and comorbidity burden, although their ability to predict clinically relevant outcomes remains uncertain.</p><p><strong>Methods: </strong>We conducted a retrospective real-world study including 172 patients with MBLD between 2016 and 2021, assessing the association of age and comorbidity burden (standardised using the Cumulative Illness Rating Scale for Geriatrics, CIRS-G score) with treatment intensity, toxicity, and clinical outcomes.</p><p><strong>Results: </strong>Treatment intensity decreased significantly with both age (p = 0.003) and CIRS-G score (p < 0.001). However, neither age nor CIRS-G score was associated with an increased rate of treatment-related toxic events. In contrast, older age was associated with worse overall survival and lower response rates (all p < 0.05), whereas CIRS-G score was not significantly associated with these outcomes. Similar associations between age and outcomes were observed in the DLBCL subgroup.</p><p><strong>Conclusion: </strong>In this real-world cohort of patients with MBLD, chronological age was more consistently associated with treatment patterns and clinical outcomes than comorbidity burden as measured by the CIRS-G score. These findings suggest that chronological age alone may not adequately capture the heterogeneity of older patients and support the use of more comprehensive assessments of frailty and functional status to inform treatment decisions.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13725099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"c-MET Inhibition Is Accompanied by PD-L1 Upregulation and Immunosuppression-Related Tumor Microenvironment Changes in Esophageal Squamous Cell Carcinoma, With Enhanced Antitumor Activity in Combination With Anti-PD-1 Therapy.","authors":"Chuan Song, Zhe Xia, Hu Wang, Xinyu Wang, Jing Li, Binbin Wang, Chen Feng, Bo Xie","doi":"10.1002/cam4.72428","DOIUrl":"10.1002/cam4.72428","url":null,"abstract":"<p><strong>Background: </strong>c-MET is implicated in ESCC progression, but whether c-MET inhibition reshapes immune checkpoint expression and the tumor immune microenvironment remains unclear.</p><p><strong>Methods: </strong>ESCC cell lines were treated with Tepotinib, and c-MET and PD-L1 expression were examined by Western blotting and immunofluorescence. MET knockdown was performed in TE-1 and KYSE150 cells. AKR syngeneic subcutaneous tumor models were used to assess PD-L1 and PD-1 expression, immune cell composition, transcriptomic and proteomic changes, NF-κB/p65 signaling, and the efficacy of Tepotinib combined with an anti-PD-1 antibody.</p><p><strong>Results: </strong>Tepotinib decreased c-MET expression and increased PD-L1 expression in ESCC cells. MET knockdown produced a similar increase in PD-L1. In vivo, Tepotinib increased PD-L1 and PD-1 expression in tumor tissues and increased PD-L1 expression in the CD45^- non-immune compartment, together with decreased CD8⁺ T cells and cDC1 cells, increased Treg cells, and increased CD206 expression in tumor-associated macrophages. Dual immunofluorescence and quantitative analysis further showed an increased proportion of CD8⁺PD-1⁺ cells among total CD8⁺ cells in Tepotinib-treated tumors. Transcriptomic and proteomic analyses indicated enrichment of inflammatory and immune-related pathways, including NF-κB, TNF, JAK-STAT, and immune checkpoint-related signaling. Tepotinib increased p65 phosphorylation, whereas NF-κB inhibition reduced p-p65 and PD-L1 expression. Tepotinib combined with anti-PD-1 antibody reduced tumor burden and delayed humane endpoint events compared with monotherapy.</p><p><strong>Conclusions: </strong>c-MET inhibition is accompanied by adaptive PD-L1 upregulation and immunosuppression-related changes in the tumor microenvironment in ESCC. NF-κB/p65 signaling may participate in this response. The enhanced antitumor activity observed with Tepotinib plus anti-PD-1 therapy supports further investigation of this combination strategy.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13724753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Study of GSDME and CXCL10 in SUV39H1-Mediated Pyroptosis and Immune Suppression in Cervical Cancer.","authors":"Li Zhang, Peiting Sheng, Dongge Cai, Ziyue Zhao, Xiaoling Wu, Yan'e Gao","doi":"10.1002/cam4.72468","DOIUrl":"10.1002/cam4.72468","url":null,"abstract":"<p><p>Cervical cancer (CC) remains a major global health challenge characterized by high incidence and mortality. The histone methyltransferase suppressor of variegation 3-9 homolog 1 (SUV39H1) has emerged as a key epigenetic regulator in tumor progression, but its role in modulating pyroptosis and remodeling of the immune microenvironment in CC remains unclear. In this study, we demonstrate that SUV39H1 promotes CC progression through dual epigenetic regulation, specifically repression of gasdermin E (GSDME) and activation of chemokine (C-X-C motif) ligand 10 (CXCL10). Overexpression of SUV39H1 in HeLa and SiHa cells enhanced histone 3 lysine 9 tri methylation (H3K9me3) deposition at the DFNA5 (GSDME) promoter, resulting in reduced transcription and suppressed GSDME-dependent pyroptosis-like cell death. Interestingly, it also upregulated CXCL10 expression. Functional assays confirmed that SUV39H1 attenuated GSDME-mediated pyroptosis-like cell death and enhanced cell migration via induction of epithelial-mesenchymal transition (EMT). Moreover, SUV39H1 drives CXCL10 secretion, which activates the chemokine (C-X-C motif) receptor 3 (CXCR3) signaling axis in macrophages and upregulates immunosuppressive molecules including programmed death ligand 1 (PD-L1), T cell immunoglobulin and mucin-domain containing-3 (Tim-3), and secreted phosphoprotein 1 (SPP1), thereby fostering an immunosuppressive tumor microenvironment (TME), and these effects appear parallel to GSDME suppression. Collectively, these findings reveal a multifaceted oncogenic role of SUV39H1 in CC, highlighting its potential as a therapeutic target for epigenetic and immunomodulatory intervention.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13725234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lifetime Hormonal Exposure and Risk of Lung Cancer in Women: Results From a French Population-Based Case-Control Study (The WELCA Study).","authors":"Youssouf Gueye, Emilie Cordina Duverger, Pascal Guénel, Marie Wislez, Jean Trédaniel, Hélène Blons, Pierre Laurent-Puig, Martine Antoine, Mireille Matrat, Loredana Radoï, Marianne Canonico","doi":"10.1002/cam4.72449","DOIUrl":"10.1002/cam4.72449","url":null,"abstract":"<p><strong>Background: </strong>With 2 million new cases annually, lung cancer is among the most frequent and the leading cause of cancer-related death worldwide. Incidence trends differ by gender, decreasing in men but increasing in women, partly due to later tobacco uptake. However, biological differences may also contribute, including the potential role of estrogen exposure. This study aimed to investigate the influence of lifetime hormonal exposure on lung cancer risk in women.</p><p><strong>Methods: </strong>WELCA is a multicenter population-based case-control study conducted in Ile-de-France between 2014 and 2017 among women aged 18-75 years. The study included 716 cases of incident primary lung cancer and 756 controls frequency-matched by age and area of residence. Information was collected through standardized questionnaires on lifestyle factors, occupational history, reproductive history, and use of exogenous hormones. Odds-ratios (OR) and confidence intervals (CI) were estimated using multivariable logistic regression models.</p><p><strong>Results: </strong>A later age at last pregnancy (≥ 33 vs. ≤ 28 years) and ever use of hormonal contraceptives was associated with a lower risk of lung cancer (OR = 0.60; 0.42-0.85 and OR = 0.57; 0.39-0.84, respectively). However, a later age at cessation of the pill use was associated with an increased risk (≥ 39 vs. ≤ 30 years: OR = 1.46; 1.06-2.03). Finally, a longer reproductive lifespan was inversely associated with lung cancer (≥ 39 vs. ≤ 36 years: OR = 0.69; 0.50-0.95).</p><p><strong>Conclusion: </strong>These findings suggest lifetime hormonal exposure may influence lung cancer risk in women. They support the hypothesis of a hormonally mediated pathway and highlight the need for further studies on sex-specific lung cancer risk.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13740371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149339954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}