Molecular Oncology最新文献

{"title":"Cancer-associated mutations in endometriosis reframe a benign disease through molecular oncology.","authors":"Clarissa Mujacic, Maria Concetta Vitale, Rita Siino, Emilia Di Giovanni, Carla Ferrante Bannera, Enrico Di Marco, Andrea Gottardo, Tancredi Didier Bazan Russo, Nadia Barraco, Alessandro Perez, Valerio Gristina, Antonio Galvano, Giuseppe Badalamenti, Antonio Russo, Viviana Bazan, Lorena Incorvaia","doi":"10.1002/1878-0261.70295","DOIUrl":"10.1002/1878-0261.70295","url":null,"abstract":"<p><p>Endometriosis is a benign yet debilitating condition, and its molecular complexity remains unexplored. Although clinically recognized, its genetic landscape has long been overlooked. This review analyses cancer-associated mutations (CAMs) identified in endometriotic lesions, revealing parallels with malignancy. Recurrent mutations in key oncogenic and tumour suppressor genes-PIK3CA, CTNNB1, KRAS, PTEN and ARID1A-emerge with patterns distinct from cancer, yet suggesting shared mechanisms. Despite the limited genomic data, these findings position endometriosis as a valuable model for investigating early tumour-like processes. By reframing endometriosis through the lens of molecular oncology, this study offers new insights into its pathogenesis and proposes a translational framework for advancing diagnostics and understanding disease progression at the benign-malignant interface.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024146","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":"Extracellular matrix remodeling and immune reprogramming drive residual tumor progression of liver cancer after incomplete microwave ablation.","authors":"Yu Liu, Yubei He, Nikolaus Berndt, Michael Mülleder, Kathrin Textoris-Taube, Jing Guo, Matthias Stechele, Justus Ramtke, Shraga Nahum Goldberg, Lynn Jeanette Savic","doi":"10.1002/1878-0261.70337","DOIUrl":"10.1002/1878-0261.70337","url":null,"abstract":"<p><p>Although microwave ablation (MWA) constitutes an effective targeted treatment for liver cancer, the mechanisms driving high recurrence rates remain poorly understood. To elucidate these processes, we established an incomplete MWA (iMWA) model in rabbit VX2 tumors and conducted proteomic profiling of residual tumors at Days 3 (D3) and 14 (D14) postablation. By integrating genomic profiles from mouse radiofrequency ablation (RFA) models, we identified 81 and 92 upregulated proteins at D3 and D14, respectively. Functional enrichment analysis (STRING and Enrichr) revealed acute injury response and extracellular matrix (ECM) remodeling predominating at D3, then markedly declining by D14. Conversely, pathways associated with signal transduction, tumorigenesis, and immune pathways were substantially upregulated at D14. Specifically, protein-protein interaction (PPI) analysis revealed that macrophage remodeling and immune checkpoint networks are functionally coupled at D14 to orchestrate an immunosuppressive microenvironment. Stouffer analysis confirmed the shift from matrix remodeling at an early stage to late-stage oncogenic signal transduction and immune suppression at progression. Overall, these findings characterize the dynamic mechanisms of postablation residual tumor growth and highlight potential therapeutic targets to inhibit protumorigenic pathways while enhancing antitumor immunity.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025224","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":"Bridging the gap: a genetically validated avian chorioallantoic membrane platform for investigation of spontaneous circulating tumor cells.","authors":"Dennis Roth, Rui P L Neves, Julia Geheb, Christian Ballmeyer, Nathalie Gaßmann, Kiki C Andree, Monica Sudarsanam, Christiane Driemel, Celine Örencik, Andrè Franken, Eslam Elmaghraby, Sven H Loosen, Roderburg Christoph, Sebastian Schoelch, Hans Neubauer, Wolfram T Knoefel, Nikolas H Stoecklein, Georg Fluegen","doi":"10.1002/1878-0261.70336","DOIUrl":"10.1002/1878-0261.70336","url":null,"abstract":"<p><p>Circulating tumor cells (CTCs) are clinically relevant markers of metastasis and prognosis in gastrointestinal (GI) cancers. However, their extreme rarity and the limitations of current in vivo models severely restrict mechanistic studies of tumor cell dissemination. Here, we demonstrate for the first time that the avian chorioallantoic membrane (CAM) assay can serve as a biologically relevant and ethically advantageous 3R-compliant (Replacement, Reduction, and Refinement) in vivo model for investigating spontaneous CTC generation. Six green fluorescent protein (GFP)-labeled human colorectal, pancreatic, and cholangiocarcinoma cell lines were xenografted onto the CAM. Using a standardized workflow, we achieved reliable detection and isolation of GFP-positive single CTCs from small-volume CAM blood samples. Critically, we reproducibly confirmed the presence of spontaneously shed CAM-derived CTCs independent of GFP expression using three established, clinically relevant CTC detection platforms. Subsequent single-cell whole-genome amplification enabled downstream short-tandem repeat (STR) profiling to authenticate CTC identity, alongside detection of tumor-specific point mutations and copy number alterations (CNAs). Isolated CTCs exhibited high genetic concordance with their parental cell lines, validating the technical robustness of our workflow and establishing the CAM assay as a versatile, scalable platform for investigating hematogenous dissemination and CTC biology outside of mammalian models. Consequently, the CAM assay opens new avenues for early mechanistic and pharmacological CTC research, including functional studies of patient-derived material.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990813","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":"SPHINX31 acts as a SRPK1 inhibitor targeting the ATR/DNA-PKcs/CHK1 replicative checkpoint to inhibit cell growth in non-small cell lung cancer.","authors":"Amani Shreim, Aurelie Genoux, Nadiia Zubchuk, Haoyang Zheng, Perla Salameh, Theo Ziegelmeyer, Fabien Dalonneau, Margot Rouchette, Christiane Oddou, Simona Miron, Helene Polveche, Adiilah Mamode Cassim, Carmen Garrido, Eleni Nikolakaki, Didier Auboeuf, Tao Jia, Sophie Zinn-Justin, Beatrice Eymin","doi":"10.1002/1878-0261.70339","DOIUrl":"10.1002/1878-0261.70339","url":null,"abstract":"<p><p>Splicing targeting drugs have emerged as promising anticancer drugs. However, their mechanisms of action remain largely unknown, notably in Non-Small Cell Lung Carcinoma (NSCLC). In this study, we demonstrated that SPHINX31, which targets SRPK1, inhibits the ATR/CHK1 signaling pathway, a cornerstone of the replicative stress response, leading to decreased cell proliferation, increased DNA damage and apoptosis, notably in NSCLC cells resistant to platinum salts. Mechanistically, we found that SRPK1 is recruited at stalled replication forks upon replicative stress, co-immunoprecipitates with the ATR/ATRIP/TOPBP1 complex, directly interacts with TOPBP1 BRCT4/5 and BRCT7/8 domains, and contributes to the accumulation of TOPBP1 nuclear foci. We further showed that SRPK1 controls the splicing of genes previously related to ATR signaling, notably WIZ. All these events are prevented by SPHINX31. Lastly, we showed that the inhibitory effects of SPHINX31 on ATR are counterbalanced by the activation of DNA-PKcs. Altogether, this study uncovers SRPK1 as a new component of the ATR/DNA-PKcs/CHK1 replicative checkpoint. SRPK1 inhibitors, alone or in combination with DNA-PKcs or CHK1 inhibitors, could provide therapeutic benefit in NSCLC patients including those who relapse after platinum-based chemotherapy.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990803","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":"Partial FAK suppression promotes tumor growth, an effect reversed by macrophage p110δ PI3K inactivation.","authors":"Lydia Xenou, Niki Tzenaki, Anna Tsapara, Maria Tzardi, Evangelia A Papakonstanti","doi":"10.1002/1878-0261.70320","DOIUrl":"10.1002/1878-0261.70320","url":null,"abstract":"<p><p>FAK/PTK2 is widely considered a therapeutic target in cancer, although its role in tumorigenesis remains context-dependent. Here, we investigated whether different degrees of FAK suppression produce distinct effects on tumor progression and whether macrophage p110δ PI3K inactivation can counteract adverse effects associated with incomplete FAK inhibition. Using MDA-MB-231 breast cancer cell clones stably transfected with FAK/PTK2-shRNA, we found that strong FAK suppression impaired tumor growth, whereas moderate FAK silencing promoted rapid tumor expansion in female and male mice. Intratumoral FAK/PTK2-siRNA inducing moderate FAK suppression similarly accelerated breast tumor growth, increased proliferation, reduced apoptosis, and increased circulating tumor cells. Transfer of macrophages expressing genetically inactive p110δ significantly reduced the tumor burden induced by moderately FAK-silenced breast cancer cells, decreased proliferation, and increased apoptosis. In melanoma tumors, suboptimal pharmacological inhibition of FAK increased tumor burden, whereas combined treatment with a selective p110δ inhibitor prevented this effect, reduced circulating melanoma cells, suppressed proliferation, and enhanced apoptosis. Since FAK inhibitors may not achieve complete and sustained inhibition of FAK activity in vivo, our findings highlight the possibility that partial FAK suppression may generate adverse biological outcomes and identify macrophage p110δPI3K as a complementary therapeutic strategy to prevent tumor-promoting consequences arising from incomplete FAK inhibition.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970216","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":"p190A/ARHGAP35 and p190B/ARHGAP5 proteins in endometrial cancer: a novel cancer-relevant paralog interplay.","authors":"Mathilde Pinault, Capucine Heraud, Mélissa Correia de Oliveira, Véronique Neaud, Valérie Valesco, Valérie Prouzet-Mauleon, Béatrice Turcq, Jean-William Dupuy, Anne-Aurélie Raymond, Sabrina Croce, Frédéric Saltel, Valérie Lagrée, Violaine Moreau","doi":"10.1002/1878-0261.70335","DOIUrl":"10.1002/1878-0261.70335","url":null,"abstract":"<p><p>Endometrial cancer is one of the main gynecological malignancies worldwide. Several studies highlight ARHGAP35 as a significantly mutated gene in these tumors. It encodes for p190RhoGAP-A (p190A), which is a major regulator of the small GTPase family of proteins. ARHGAP5 is a paralog of ARHGAP35 that encodes p190RhoGAP-B (p190B). By analyzing human endometrial cancer samples, we found a co-occurrence of mutations in ARHGAP35 and ARHGAP5 genes and reported that both are less expressed at the mRNA level in tumoral samples compared to healthy tissues. We then studied the impact of p190A/B under-expression in endometrial cancer and the relationship between the two paralogs. We generated CRISPR/Cas9-mediated HEC-1-A knockout cells for p190A and p190B. We showed that removal of each paralog led to a similar actin remodeling phenotype with the formation of Cross-Linked Actin Networks (CLANs), dependent on the Rho/ROCK pathway. Moreover, proteomic analysis of p190A and p190B knockout cells highlighted similar affected cell functions. Finally, our study demonstrates a functional interaction between p190A and p190B where removal of both paralogs is deleterious in endometrial cancer cells, unveiling a potential actionable vulnerability.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920094","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":"Paclitaxel induces NM2-dependent cellular contraction through GEF-H1 dissociation from microtubules and RhoA/ROCK activation in cancer cells.","authors":"Gloria Asensio-Juárez, Rafael Pérez-Díaz, Hugo Ramos-Solano, Marina Garrido-Casado, Vanessa C Talayero, Miguel Vicente-Manzanares","doi":"10.1002/1878-0261.70333","DOIUrl":"10.1002/1878-0261.70333","url":null,"abstract":"<p><p>In this study, we have investigated the crosstalk between microtubule dynamics and actomyosin contractility in cancer cells treated with taxanes, which are chemotherapeutic agents used to treat solid tumors. We found that paclitaxel (PTXL) induced cell contraction through a mechanism that involved the rapid dissociation of GEF-H1 from microtubules, and the phosphorylation and acute activation of NM2 in a RhoA-dependent manner. Mutation of a major α-tubulin regulatory site (K40R) markedly slowed and reduced the efficiency of PTXL-induced GEF-H1 dissociation, indicating that this site is required for the full, rapid release of GEF-H1 from the microtubule lattice. Inhibitors of tubulin deacetylase HDAC6 promoted a slow release of GEF-H1 from microtubules and a lagged accumulation of phosphorylated NM2. Unexpectedly, depletion of tubulin acetyltransferase αTAT1 also induced NM2 phosphorylation, indicating that microtubule acetylation is involved in the maintenance of contractile homeostasis. Together, these results indicate that PTXL induces rapid cellular contraction dependent on the GEF-H1-RhoA-ROCK axis, in which K40 of α-tubulin gates the efficiency of GEF-H1 dissociation from microtubules, whereas homeostatic, αTAT1-dependent microtubule acetylation maintains appropriate levels of cellular contractility through long-term control of NM2 phosphorylation and actomyosin organization.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920238","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":"APOBEC3 activity and DNA polymerase-ε deficiency are associated with distinct IDH1 R132 hotspot mutations.","authors":"Kelly E Butler, Bilal A Lone, Ecem Unal, A Rouf Banday","doi":"10.1002/1878-0261.70334","DOIUrl":"10.1002/1878-0261.70334","url":null,"abstract":"<p><p>IDH1 R132 mutations are among the most frequent hotspot mutations in cancer, but their mutational origins have remained unclear. Here, we provide evidence that IDH1 R132C, the predominant IDH1 mutation in cholangiocarcinoma, acute myeloid leukemia, and melanoma, likely arises through APOBEC3-mediated mutagenesis, specifically by APOBEC3A or APOBEC3B. IDH1 R132C is a TpC>TpT substitution on the lagging-strand DNA template within a hairpin-forming sequence context, consistent with APOBEC3 susceptibility. In vitro assays showed that APOBEC3A and APOBEC3B can deaminate the relevant cytosine, while APOBEC3A and APOBEC3B expression patterns in tumor types with recurrent IDH1 R132C were consistent with their potential involvement in generating this mutation. IDH1 R132G, a TpC>TpG substitution at the same site, may similarly result from APOBEC3A or APOBEC3B activity. By contrast, IDH1 R132H, the predominant IDH1 mutation in lower grade glioma and glioblastoma, is a CpG>TpG substitution at a methylated cytosine on the leading-strand DNA template, a pattern more consistent with DNA polymerase epsilon replication error. Concordantly, tumor types enriched for IDH1 R132H showed relatively low POLE expression. Together, these in vitro and bioinformatic analyses provide insight into the distinct mutational mechanisms that likely underlie recurrent IDH1 hotspot mutations in cancer.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920111","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":"Predictive and prognostic biomarkers of Bacillus Calmette-Guérin therapy failure in bladder cancer patients: A systematic review.","authors":"Rui Ribeiro-Pereira, Ana Teixeira-Marques, Rui Freitas, João A Carvalho, Sara Monteiro-Reis, Giorgio I Russo, Rui Henrique, Carmen Jerónimo","doi":"10.1002/1878-0261.70329","DOIUrl":"10.1002/1878-0261.70329","url":null,"abstract":"<p><p>High-risk non-muscle invasive bladder cancer (NMIBC) is a common urological malignancy with a high propensity for recurrence (30-40% of patients) despite treatment with Bacillus Calmette-Guérin (BCG) instillations. Identifying patients who are likely to respond or not to BCG therapy before treatment initiation may significantly improve patient outcomes and minimise unnecessary treatments. This systematic review critically assessed the existing literature on the potential of non-invasive biomarkers to predict BCG failure in NMIBC patients. A comprehensive bibliographic search on PubMed, Scopus and Medline databases was conducted to identify relevant studies published up to July 7, 2025. After a thorough screening and selection process, 72 studies were included in the final analysis, 58 of which focused on prognostic markers, 6 on predictive markers, and 8 examined both. Moreover, 55 studies focused on tissue, while 28 studied liquid biopsy-derived biomarkers, showcasing their ability to reflect the dynamic characteristics of the tumour and its microenvironment. The most frequently studied biomarkers comprised p53, Ki-67 and pRB. Furthermore, several immunological markers were also explored, highlighting the current challenge of BCG therapy prediction biomarkers. Despite its valuable insights, this systematic review faced limitations within the included studies, such as issues related to reproducibility, feasibility, and small sample sizes. Nonetheless, the findings indicate that a wide array of molecules show potential as prognostic and/or predictive markers for BCG failure, which may improve the clinical management of this complex disease.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900962","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":"Gut microbiota alterations in patients with non-small-cell lung cancer undergoing chemoradiotherapy.","authors":"Hanne Marte Nymoen, Zhi Zhao, Henrik Horndalsveen, Maria Moksnes Bjaanæs, Bjørn Henning Grønberg, Tarje Halvorsen, Tesfaye Madebo, Marianne Aanerud, Jussi Koivunen, Kersti Oselin, Saulius Cicenas, Nina Helbekkmo, Jarkko Ahvonen, Maria Silvoniemi, Tine Norman Alver, Tonje Dalen, Åsa Kristina Öjlert, Saima Jamil Farooqi, Åslaug Helland, Vilde Drageset Haakensen","doi":"10.1002/1878-0261.70326","DOIUrl":"10.1002/1878-0261.70326","url":null,"abstract":"<p><p>Growing evidence suggests that gut microbial features may predict-and potentially modulate-responses to cancer therapy, particularly immunotherapy. However, the impact of concurrent chemoradiotherapy (CRT) on the gut microbiota remains less well-understood. This knowledge gap is especially relevant in locally advanced non-small-cell lung cancer (NSCLC), where CRT typically precedes immunotherapy. We therefore investigated whether CRT alters gut microbial composition and whether such changes are associated with survival outcomes. Fecal samples were collected at three time points: prior to CRT (baseline), at completion of CRT, and immediately before initiation of consolidation immunotherapy, from 62 patients with locally advanced NSCLC. Microbiota profiling was performed using a qPCR-based panel (PMP™) targeting 108 prevalent microbial taxa. Within-sample (alpha) and between-sample (beta) bacterial diversity were assessed across time points and clinical subgroups defined by antibiotic exposure and survival outcomes. Alpha diversity remained stable from baseline to completion of CRT (all P > 0.60). Patients who received broad-spectrum antibiotics during CRT had significantly lower alpha diversity compared with those who did not receive antibiotics (P = 0.017), reflecting a transient between-group difference. Beta diversity differed modestly but significantly at baseline between survival groups (progression-free survival ≥ 18 vs < 18 months; PERMANOVA R² = 0.028, P = 0.045). The gut microbiota appears largely stable during CRT for locally advanced NSCLC but is susceptible to disruption by antibiotic use. Baseline beta diversity differences between survival groups may signal a potential role for gut microbial composition as a future preliminary biomarker and warrant further investigation.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900932","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}