Oncology Research最新文献

{"title":"The Impact of Combretastatin A-4 on Cancer Cells and Circulating Tumor Cells (CTCs): A Multi-Assay Approach.","authors":"Dimitrios Papakonstantinou, Vasileios Vardas, Despoina M Varouhaki, Aikaterini Kotzamouratoglou, Karolina Mangani, Julia A Ju, Catherine Alix-Panabières, Stuart S Martin, Constantinos M Athanassopoulos, Galatea Kallergi","doi":"10.32604/or.2026.085665","DOIUrl":"10.32604/or.2026.085665","url":null,"abstract":"<p><p><b>Objectives:</b> Combretastatin A-4 (CA-4) is a microtubule-disrupting agent with established anti-tumor properties. This study aimed to evaluate the effects of CA-4 on key metastatic traits of cancer cells, including migration, clonogenic potential, cytoskeletal protein expression, and microtentacle (McTN) formation, using multiple cancer cell models, including the colon patient-derived circulating tumor cell line CTC-MCC-41. <b>Methods:</b> H1299 (non-small cell lung cancer), MDA-MB-231 (triple-negative breast cancer), HT-29 (colorectal cancer), and CTC-MCC-41 (derived from the blood of a colon cancer patient) cells were treated with CA-4 (10 μM) for 24 and 48 h. Colony formation was assessed with a clonogenic assay. Migration assays (Boyden chamber) evaluated cell motility, while cell viability was determined via MTT assay. Western blot analysis examined vimentin and α/β-tubulin expression. TetherChip assay analyzed McTN formation using wheat germ agglutinin (WGA) staining. <b>Results:</b> CA-4 treatment significantly reduced cell viability, colony formation, and migration across all tested cancer cell lines. Western blot analysis revealed a marked reduction in vimentin and α/β-tubulin expression after 48 h of treatment, indicating disruption of cytoskeletal integrity. In addition, TetherChip analysis demonstrated a pronounced decrease in McTN formation following CA-4 exposure, suggesting inhibition of cytoskeletal protrusions associated with metastatic dissemination. <b>Conclusions:</b> CA-4 effectively impairs multiple cancer cell functions related to metastatic progression, including proliferation, migration, cytoskeletal organization, and McTN formation. These findings highlight the potential of CA-4 as a microtubule-targeting agent with anti-metastatic activity, particularly in circulating tumor cells.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"1"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Polymerase θ Drives Colorectal Cancer Progression through Wnt/β-Catenin Activation and Shows Potential Association with Immunosuppressive Microenvironment Remodeling.","authors":"Li Li, Jianhua Wang, Feilong Zhou, Lingjun Geng, Kongwang Hu","doi":"10.32604/or.2026.080204","DOIUrl":"10.32604/or.2026.080204","url":null,"abstract":"<p><p><b>Background:</b> Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with limited treatment options for advanced-stage patients. DNA polymerase theta (POLQ) is overexpressed in various cancers, but its role and underlying mechanisms in CRC remain not fully elucidated. This study aimed to investigate the expression, prognostic value, biological functions, and molecular mechanisms of POLQ in CRC. <b>Methods:</b> POLQ expression was analyzed using public databases and 55 paired clinical samples. Lentivirus-mediated knockdown and overexpression were employed to assess CRC cell proliferation, migration, and invasion. Single-cell transcriptomics and CellChat analysis were used to explore the tumor microenvironment (TME). Western blotting, immunofluorescence, and dual-luciferase reporter assays were performed to verify the Wnt/β-catenin pathway and epithelial-mesenchymal transition (EMT). <b>Results:</b> POLQ was significantly overexpressed in CRC tissues and cell lines, and high POLQ expression was associated with neural invasion, vascular tumor thrombus, lymph node metastasis, advanced TNM stage, and poor prognosis. Single-cell analysis revealed that POLQ was specifically enriched in malignant epithelial cells, which acted as communication hubs with prominent Wnt signaling. Functional experiments demonstrated that POLQ activated the Wnt/β-catenin pathway, induced EMT, promoted β-catenin nuclear translocation and TCF/LEF transcriptional activity, and enhanced CRC cell proliferation, migration, and invasion. The Wnt inhibitor XAV939 reversed the POLQ overexpression-induced malignant phenotype, while the Wnt activator SKL2001 partially rescued the knockdown phenotype. Additionally, single-cell transcriptomics and CellChat analysis generated a computational prediction that POLQ-high cells may be involved in remodeling of the immunosuppressive microenvironment; however, this inference requires direct experimental validation through immune cell profiling in future studies. <b>Conclusions:</b> POLQ promotes CRC progression by activating the Wnt/β-catenin-EMT axis. Bioinformatic inference suggests a potential association with an immunosuppressive microenvironment, but this finding remains correlative and requires experimental confirmation. These findings suggest that POLQ is a potential prognostic biomarker and therapeutic target, though further validation in prospective, multicenter cohorts is warranted.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"20"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Programmed Cell Death in Urological Cancers: Orchestrating the Immune Microenvironment and Immunotherapy.","authors":"Zhenyang Ye, Jinyang Luo, Ying Zhang, Longhua Lu, Min Lei, Shi Deng","doi":"10.32604/or.2026.087565","DOIUrl":"10.32604/or.2026.087565","url":null,"abstract":"<p><p>Programmed cell death regulates the tumor immune microenvironment. A comprehensive synthesis of how multiple programmed cell death pathways collectively orchestrate the remodeling of the urological immune landscape is currently lacking. This review summarizes and discusses how diverse programmed cell death modes, including ferroptosis, pyroptosis, autophagy, PANoptosis, necroptosis and cuproptosis, regulate immune evasion or activation in a context-dependent manner. Current preclinical evidence suggests that necroptosis, pyroptosis, and cuproptosis may enhance anti-tumor immunity by facilitating the release of damage-associated molecular patterns and increasing the infiltration of functional CD8⁺ T cells and dendritic cells, thereby potentially improving responses to immunotherapy. At the same time, several programmed cell death pathways display exhibit pronounced context dependence. In renal cell carcinoma, ferroptosis exhibited a functional contradiction: while its induction directly eliminated cancer cells, the resulting lipid peroxidation could simultaneously impair the survival and metabolic fitness of infiltrating immune cells. This dualistic effect necessitated precise, cell-type-specific strategies to ensure that ferroptosis-mediated tumor suppression did not undermine the anti-tumor immune response. Similarly, autophagy in tumor cells facilitated immune evasion via the selective degradation of major histocompatibility complex class I (MHC-I) and stabilizing programmed death-ligand 1, while it also improved the cytotoxic function and cellular longevity of natural killer cells. Consequently, future drug development should consider cell-type-specific modulation to address these contradictory effects across different cells and avoid unintended immunosuppression. Emerging evidence on PANoptosis, which integrates multiple programmed cell death pathways into a synergistic framework, may provide a useful direction for investigating immune therapeutic resistance. Ultimately, targeting the intricate landscape of programmed cell death may inform strategies for improving cancer treatment and urological immunotherapy, but stronger translational evidence is still needed.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"11"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Malignant T Cells as Determinants of Immunotherapeutic Response in Chronic Lymphocytic Leukemia: Towards Personalized Strategies.","authors":"Agata Kosmaczewska, Lidia Ciszak","doi":"10.32604/or.2026.081365","DOIUrl":"10.32604/or.2026.081365","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia (CLL) is a biologically heterogeneous B cell malignancy in which non-malignant T lymphocytes constitute a critical component of the tumor microenvironment and significantly influence disease evolution and the therapeutic response. Growing evidence suggests that CLL-associated T cells not only participate in the antitumor response but also activate signals that promote the development of CLL subclones. Although novel targeted therapies, such as Bruton's tyrosine kinase (BTK) inhibitors, BTK degraders, B-cell lymphoma 2 (BCL-2) inhibitors, T cell engagers, immune checkpoint inhibitors, and adoptive T cell therapy have different mechanisms of action, they affect the T cell compartment in addition to targeting CLL cells. Therefore, in-depth knowledge of the role of T cells in the development and progression of CLL is essential for proper stratification of the benefit-to-risk ratio with regard to immunotherapeutic strategies. This review comprehensively summarizes current knowledge on alterations within the T cell compartment in CLL and discusses the clinical implications, regarding clinical course and response to immunotherapy.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"7"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNAs in Plasma and Beyond: Potential Biomarkers for Breast Cancer.","authors":"Chunming Wang, Xu Wang, Yubo Liu, Jia Xu, Pingfa Li","doi":"10.32604/or.2026.085395","DOIUrl":"10.32604/or.2026.085395","url":null,"abstract":"<p><p>Breast cancer (BC) continues to be a major cause of cancer-related mortality among women, and early diagnosis remains critical for improving survival outcomes. Conventional tissue biopsy and imaging techniques are constrained by invasiveness and limited sensitivity in early-stage disease, whereas routine serum tumor markers lack sufficient specificity for reliable early detection. Circular RNAs (circRNAs) have increasingly been recognized as promising non-invasive biomarkers, owing to their remarkable stability and detectability in plasma. Here, we summarize the current landscape of plasma circRNAs as diagnostic, prognostic, and chemoresistance-related biomarkers in BC, emphasizing their clinical relevance in therapy selection, subtype stratification, treatment monitoring, and recurrence prediction. Aberrant circRNA expression in the plasma of BC patients has been associated with tumor size, stage, and molecular subtype, and functionally linked to cell survival, metastasis, and drug resistance. Importantly, circRNAs may complement conventional approaches including imaging and serum markers, and their integration with other circulating analytes could enhance diagnostic precision and support individualized therapeutic decisions. Our work consolidates recent advances in circRNA research across preoperative, postoperative, drug resistance, and recurrence settings, providing a framework for non-invasive diagnosis, clinical decision-making, and outcome prediction in BC management. This review aims to bridge tissue-based discoveries and plasma-based applications for the clinical translation of circRNAs.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"13"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Tumor Biology to Clinical Perspectives: Novel Biomarkers and Therapeutic Insights in Gastric Cancer.","authors":"Xiya Cheng, Yunshu Ma, Jinglu Yan, Yizhe Zhang, Riguge Su, Xiaoming Tao, Jing Zhao, Peizhun Du","doi":"10.32604/or.2026.083832","DOIUrl":"10.32604/or.2026.083832","url":null,"abstract":"<p><p>Gastric cancer (GC) is a leading cause of cancer-related mortality worldwide. Accurate early detection, timely diagnostic stratification, and robust prognostic risk assessment are essential for optimizing clinical outcomes and improving survival duration. However, conventional serological biomarkers demonstrate limited diagnostic performance owing to suboptimal sensitivity and specificity, while standard chemotherapy and targeted therapies provide only modest survival benefits in GC. Marked inter- and intratumoral heterogeneity further characterizes GC as a biologically complex and treatment-resistant malignancy. To date, significant progress has been made in comprehensively delineating the complex molecular pathogenesis of GC, providing a strong rationale for the development of novel biomarkers and promising therapeutic targets. The aim of this review is to systematically summarize recent advances ranging from aberrant genetic and epigenetic alterations; dysregulation of oncogenic signaling pathways; sophisticated crosstalk within the tumor microenvironment; intricate microbiota-inflammation interactions; fundamental discoveries to potential clinical translation, including novel biomarkers for early detection, diagnosis and prognostic stratification; and emerging therapeutic strategies for GC. Collectively, this work provides a conceptual framework for advancing precision medicine in GC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"12"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholesterol Metabolism in Cancer Patients: Mechanisms, Treatment-Related Effects, and Cardio-Oncology Management.","authors":"Mariagrazia Piscione, Barbara Pala, Francesco Cribari, Paola Gualtieri, Dario Gaudio, Marco Alfonso Perrone, Laura Di Renzo","doi":"10.32604/or.2026.079215","DOIUrl":"10.32604/or.2026.079215","url":null,"abstract":"<p><p>Cholesterol metabolism is central to cancer biology, influencing tumour initiation, progression, and therapeutic response, while contributing to the increased cardiovascular risk observed in cancer patients. Epidemiological studies investigating the relationship between circulating cholesterol levels and cancer risk have yielded conflicting results, reflecting substantial biological heterogeneity, tumour-specific metabolic demands, and methodological biases such as reverse causality. At the cellular level, malignant cells exhibit elevated cholesterol uptake and synthesis to sustain membrane biogenesis, lipid raft-dependent oncogenic signalling, and rapid proliferation. Cholesterol and its oxidized derivatives further modulate inflammation, angiogenesis, immune evasion, and key signalling pathways. Anticancer therapies profoundly disrupt lipid homeostasis; conventional chemotherapies, targeted therapies, hormone-modulating agents, and immunotherapies can induce dyslipidaemia and accelerate atherosclerotic disease, thereby contributing to long-term morbidity in cancer survivors. Conversely, lipid-lowering therapies-particularly statins-have emerged as pivotal tools in cardio-oncology, primarily for cardiovascular protection. Beyond this role, growing evidence suggests potential adjunctive antitumor effects mediated through inhibition of the mevalonate pathway, blockade of oncogenic signalling, and modulation of the tumour microenvironment. Novel agents, including ezetimibe, bempedoic acid, and proprotein convertase subtilisin-kexin type 9 inhibitors, provide additional therapeutic options, with emerging evidence supporting their immunomodulatory and anticancer properties, especially in combination with immune checkpoint inhibitors. Cholesterol metabolism plays a critical role in both CV disease and cancer biology, with growing evidence suggesting a complex bidirectional relationship between lipid homeostasis and tumour development. In addition, several anticancer therapies may profoundly affect lipid metabolism, thereby contributing to CV risk in cancer patients. The aim of this review is to provide a comprehensive overview of the interplay between cholesterol metabolism and cancer, to summarize the lipid-modifying effects of anticancer therapies, and to discuss the potential role of lipid-lowering strategies within the evolving framework of cardio-oncology care.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"4"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Destabilization of hsa_circ_0015508 by YTHDF2 Enhances miR-496-Mediated FOXN3 Suppression to Drive Nasopharyngeal Carcinoma Progression.","authors":"Aiyu Ma, Xu Wang, Lu Lu, Shuaijie Wang, Qiuyu Zhao, Xuemei Zhang, Yiping Sun, Xuan Meng, Yan Zhang, Yuzhong Yang, Jinhua Zheng, Xiang Zheng","doi":"10.32604/or.2026.084662","DOIUrl":"10.32604/or.2026.084662","url":null,"abstract":"<p><p><b>Objectives:</b> YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2) had been implicated in nasopharyngeal carcinoma (NPC) progression. Increasing evidence indicated that numerous circular RNAs (circRNAs) were involved in regulating tumor progression. However, how the regulation of circRNAs by YTHDF2 contributes to NPC progression remains to be uncovered. In this study, we aimed to elucidate the role and mechanism of YTHDF2-mediated circRNA regulation in NPC migration and invasion. <b>Methods:</b> YTHDF2 expression in NPC was assessed using GEO datasets and immunohistochemistry. Functional experiments were performed in HNE1 and 5-8F cells, with migration/invasion evaluated by wound healing and transwell assays, and epithelial-mesenchymal transition (EMT) markers by Western blotting. CircRNA candidates were screened through circRNA sequencing. CircRNA m6A modification was assessed by methylated RNA immunoprecipitation-quantitative PCR (MeRIP-qPCR). The SELECT method (single-base elongation- and ligation-based qPCR amplification) was used to identify the specific m6A modification site. RNA stability was measured by actinomycin D assay. circRNA-miRNA and miRNA-target interactions were validated by luciferase reporter assays. <b>Results:</b> YTHDF2 expression was upregulated in NPC tissues and was found to promote <i>in vitro</i> migration and invasion phenotypes. Mechanistically, m6A-modified <i>circ_0015508</i> was recognized and degraded by YTHDF2. YTHDF2-mediated pro-migration and pro-invasion effects were reversed by <i>circ_0015508</i>. <i>FOXN3</i> was identified as a target of <i>miR-496</i>. <i>Circ_0015508</i> was found to sequester <i>miR-496</i>, thereby de-repressing <i>FOXN3</i> expression. <b>Conclusion:</b> In this study, a potential oncogenic pathway was delineated in which NPC migration and invasion were facilitated by YTHDF2 via degradation of <i>circ_0015508</i>, thereby the sponging effect of <i>miR-496</i> was abolished and <i>FOXN3</i> expression was suppressed.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"26"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy in Bellini Duct Carcinoma: A Systematic Review.","authors":"Antonio David Lázaro-Sánchez, Javier David Benítez-Fuentes, Sofía Wikström-Fernández, María Nevado-Rodríguez, Pablo Conesa-Zamora, Ginés Luengo-Gil, Alejandra Ivars-Rubio, Marta Zafra-Poves, Edgardo D Carosella, Belén Fernández-Molina, Andrés Nieto-Olivares, María José Sánchez de Las Matas Garre, Ana Belén Arroyo","doi":"10.32604/or.2026.081674","DOIUrl":"10.32604/or.2026.081674","url":null,"abstract":"<p><p><b>Background:</b> Collecting duct carcinoma (CDC; Bellini duct carcinoma) is a rare, aggressive renal cancer with no established standard of care, and evidence for immune checkpoint inhibitor (ICI)-based therapy in CDC remains emerging and fragmented. We aimed to systematically synthesise efficacy and safety data on immunotherapy in adult patients with CDC. <b>Methods:</b> PubMed and Web of Science were searched from inception to 29 March 2025, with targeted post-search monitoring of key journals and ClinicalTrials.gov updated on 11 April 2026. Prospective interventional studies, observational cohorts/registries, and case series/reports were eligible. Screening, extraction and risk-of-bias appraisal (Joanna Briggs Institute tools) were performed independently in duplicate; results were narratively synthesised. <b>Results:</b> Overall, ICIs-particularly combinations-showed clinically meaningful activity in a subset of CDC patients. Twenty-four studies met criteria (2 prospective trials, 8 observational cohorts, 14 case-level publications/16 patients). The SUNNIFORECAST randomised phase II trial reported a CDC-specific ORR of 40% with ipilimumab + nivolumab versus 20% with standard of care (n = 9 CDC). Observational evidence yielded ORR ~10-44% and mOS ~13-42 months depending on regimen, with the highest activity seen with ICI plus TKI combinations. Durable complete responses (≥3-6 years) were documented at case level with dual checkpoint blockade and anti-PD-1 monotherapy. Safety was generally manageable, though serious events occurred sporadically (immune-mediated hepatitis; one fatal pneumonia). <b>Conclusions:</b> ICIs-particularly combination strategies-demonstrate clinically meaningful activity in selected patients with CDC, but evidence is limited by small samples, heterogeneity and high risk of bias. Prospective, biomarker-informed CDC-dedicated trials and coordinated registries are needed.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"2"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy Inhibition Enhances the Antitumor Efficacy of MET Targeting in MET-High Pancreatic Cancer.","authors":"Zhiyi Min, Chunbin Wang, Tongjin Yin, Wanyan Jiao, Dandan Zhou, Xuyao Zhang, Junli Cui, Zhe Ding","doi":"10.32604/or.2026.084396","DOIUrl":"10.32604/or.2026.084396","url":null,"abstract":"<p><p><b>Objectives:</b> MET inhibitors have demonstrated clinical efficacy in several MET-driven malignancies; however, their therapeutic potential in pancreatic cancer remains insufficiently characterized. This study aimed to evaluate the antitumor activity of the selective MET inhibitor savolitinib in MET-high pancreatic cancer and to investigate the role of autophagy in the cellular response to MET inhibition. <b>Methods:</b> MET-high pancreatic cancer cell lines (AsPC-1 and BxPC-3) were treated with savolitinib. Cell viability, apoptosis, transcriptomic profiling, and signaling pathway analyses were performed to characterize its antitumor effects and underlying mechanisms. Autophagy induction was assessed using monodansylcadaverine (MDC) staining, transmission electron microscopy, lysosomal co-localization analysis, and western blotting of autophagy-related markers. The therapeutic efficacy of combining savolitinib with the autophagy inhibitor chloroquine was further evaluated <i>in vitro</i> and in BxPC-3 xenograft models. <b>Results:</b> Savolitinib significantly inhibited MET phosphorylation and reduced the viability of MET-high pancreatic cancer cells while inducing apoptosis, as evidenced by increased levels of cleaved PARP, cleaved caspase-3, and an elevated Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio. Transcriptomic analysis revealed significant enrichment of autophagy-related pathways among savolitinib-responsive genes. Savolitinib induced autophagy-associated vesicular changes and autophagic flux, accompanied by suppression of AKT/mTOR signaling. Pharmacological inhibition of autophagy with chloroquine markedly enhanced savolitinib-induced apoptosis <i>in vitro</i> and significantly improved tumor growth inhibition <i>in vivo</i>, achieving a tumor growth inhibition rate of 84.96% in the combination-treatment group without obvious systemic toxicity under the tested conditions. <b>Conclusion:</b> Savolitinib-induced autophagy functions as an adaptive cytoprotective response in MET-high pancreatic cancer. Combined inhibition of MET and autophagy enhances antitumor activity and warrants further evaluation in MET-high pancreatic cancer models.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"21"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}