Clinical & Translational Oncology最新文献

{"title":"Driver mutation profiling by next-generation sequencing predicts survival and recurrence after curative-intent resection for pancreatic ductal adenocarcinoma: a genomic cohort study.","authors":"Muhammad Maisam Ali, Kaniala K Aragon, Benjamin A Cher, Kaleem S Ahmed, Clayton T Marcinak, Alexandra W Acher, Jeremy Kratz, Muhammed Murtaza, Mark E Burkard, Syed Nabeel Zafar","doi":"10.1007/s12094-026-04564-6","DOIUrl":"https://doi.org/10.1007/s12094-026-04564-6","url":null,"abstract":"<p><strong>Background: </strong>Next-generation sequencing (NGS) is standard practice in metastatic pancreatic ductal adenocarcinoma (PDAC), yet its prognostic utility in patients undergoing curative-intent resection remains poorly defined. Characterizing whether driver mutations independently influence post-surgical outcomes [overall survival (OS), time-to-recurrence (TTR), and pathological response (PR)] may inform perioperative risk stratification and patient selection for emerging targeted therapies.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of adults undergoing pancreatectomy for PDAC at a single high-volume academic center (2016-2025), with concurrent NGS profiling. Clinicopathologic and genomic data (KRAS, TP53, CDKN2A, SMAD4, and BRCA2 mutations) were obtained from an integrated institutional data commons. OS and TTR were evaluated using Kaplan-Meier analysis and multivariable Cox proportional hazards regression. PR (College of American Pathologists grade 0-1) was assessed using logistic regression.</p><p><strong>Results: </strong>Of 188 eligible patients (median age: 66; 42.5% female), 83.5% received neoadjuvant chemotherapy and 12.8% achieved major pathological response. KRAS was the most prevalent mutation (84.6%), followed by TP53 (61.7%), CDKN2A (33.0%), SMAD4 (18.1%), and BRCA2 (3.2%). Median TTR and OS were 10.8 and 27.1 months, respectively. In multivariable analysis, TP53 mutation was associated with shorter OS (HR, 1.65 95% CI 1.02-2.66), and CDKN2A mutation with shorter TTR (HR 1.69, 95% CI 1.19-2.39). KRAS was associated with poorer PR compared to wild type (OR 4.45, 95% CI 1.26-15.65).</p><p><strong>Conclusion: </strong>In this exploratory analysis, TP53 and CDKN2A mutations were independently associated with poorer outcomes post-PDAC resection, supporting the potential of upfront NGS for perioperative risk stratification. Prospective, multicenter validation is needed to establish clinical utility.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EML4-ALK fusion rewires transcriptomic, miRNA, and CAF-associated programs in non-small cell lung cancer.","authors":"Divya Mishra, Shivangi Agrawal, Divya Malik, Ekta Pathak, Rajeev Mishra","doi":"10.1007/s12094-026-04569-1","DOIUrl":"https://doi.org/10.1007/s12094-026-04569-1","url":null,"abstract":"<p><strong>Purpose: </strong>This study presents an integrative analysis of paired mRNA/miRNA expression and tumor microenvironment features to characterize the molecular landscape associated with EML4-ALK fusion status in non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>Using TCGA-derived fusion-positive and fusion-negative NSCLC cohorts, we compared three complementary layers of tumor biology: transcriptomic architecture, miRNA-mRNA regulatory networks, and immune-stromal composition.</p><p><strong>Results: </strong>Fusion-positive tumors exhibited a distinct molecular program characterized by metabolic and proteostasis reprogramming, including glycolytic and N-glycan biosynthetic pathways linked to endoplasmic reticulum protein processing and export. Relative to fusion-negative tumors, they also showed reduced stromal infiltration and attenuation of extracellular matrix, adhesion, calcium signaling, and cytokine-related transcriptional programs. Integrative miRNA analysis identified a fusion-associated, miR-3065-centered regulatory hub with predicted extracellular matrix- and adhesion-related targets,including PDGFRB, CTSK, COL4A2, SPARC, FBN1, and LUM, whereas fusion-negative tumorsshowed miRNA network alterations associated with proliferative and ciliary programs. Tumormicroenvironment analysis further distinguished the groups, with fusion-positive tumors showing reduced cancer-associated fibroblast infiltration.</p><p><strong>Conclusion: </strong>These findings characterize distinct molecular and microenvironmental features associated with EML4-ALK fusion-positive NSCLC and identify candidate regulatory networks and biomarkers that, pendingvalidation, may inform subtype-specific therapeutic stratification.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical recommendations for exercise and nutrition in patients with lung cancer.","authors":"Ana Cardeña-Gutiérrez, Teresa García-Manrique, Laura Gutiérrez-Sainz, Paola Gonzalo-Encabo, Juan Manuel Guardia-Baena, Antonio José Montes Ruiz, Raúl Hernanz de Lucas, Ana María Soler Garrigós, José María Matilla González, Luis León-Mateos, Margarita Majem, Raquel Sebio Garcia, Raquel Pérez García","doi":"10.1007/s12094-026-04571-7","DOIUrl":"https://doi.org/10.1007/s12094-026-04571-7","url":null,"abstract":"<p><p>Lung cancer (LC) is the leading cause of cancer mortality worldwide. Beyond pharmacological advances, lifestyle interventions such as exercise and nutrition have emerged as valuable adjuvant strategies. Preclinical and translational studies suggest that exercise may modulate molecular and immune pathways relevant to tumor biology, whereas clinical studies support benefits in functional capacity, symptom burden, and quality of life in selected patients with LC. In surgical candidates, prehabilitation focusing on exercise and nutritional optimization improves postoperative outcomes; in unresectable or advanced stages, exercise maintains functionality and mitigates symptoms. Nutritional intervention is critical because malnutrition and sarcopenia are common and negatively affect prognosis. Early screening with tools followed by structured nutritional support, including oral nutritional supplements or, when clinically indicated, enteral nutrition, is recommended. Mediterranean dietary patterns have been associated with a lower risk of cancer, including LC, whereas evidence for improved clinical outcomes after an LC diagnosis remains limited. This narrative review summarizes the physiological rationale, clinical evidence, and practical application of exercise and nutritional interventions across the lung cancer care pathway, while distinguishing direct clinical evidence from preclinical and indirect evidence.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of pre-intervention circulating cytokines in digestive system cancers: a systematic review and meta-analysis.","authors":"Fatemeh Tajik, Fereshteh Rezagholizadeh, Mahdieh Razmi, Sadegh Safaei, Mojgan Alaeddini, Shahroo Etemad-Moghadam, Leila Eini","doi":"10.1007/s12094-026-04566-4","DOIUrl":"https://doi.org/10.1007/s12094-026-04566-4","url":null,"abstract":"<p><strong>Background: </strong>Circulating cytokines can influence tumor progression and immune evasion, serving as non-invasive biomarkers in digestive system (DS) cancers. This study evaluates the prognostic significance of biofluid cytokines in DS cancers.</p><p><strong>Methods: </strong>Comprehensive literature search in various databases identified studies reporting the prognostic importance of serum or plasma cytokines based on multivariate data, focusing on overall survival (OS) and disease/relapse/progression-free/cancer-specific-survivals (DFS/RFS/PFS/CSS). Quality assessment was done using the Newcastle-Ottawa scale. Heterogeneity was evaluated through Chi-square-based Q and I2 analyses. Publication bias was assessed via funnel plots, Egger's, Begg's, and trim-and-fill methods, alongside subgroup and sensitivity analyses.</p><p><strong>Results: </strong>A total of 42 articles evaluating 7 blood cytokines in DS cancers were included, with IL-6 and the CXCL family being the most studied. Elevated IL-6 levels were significantly associated with poor survival outcomes in esophageal, hepatocellular, biliary tract, pancreatic, and colorectal cancers for both OS and DFS/RFS/PFS/CSS. High CXCL levels correlated with worse prognosis in colorectal (OS: HR = 2.019) and hepatocellular (OS: HR = 5.569, DFS/RFS/PFS/CSS: HR = 1.610) cancer patients. Higher CCL levels predicted poor OS (HR = 1.912) in colorectal cancer. Circulating IL-10, IL-1β, and TNF-α showed no significant correlation with survival outcomes in DS. Subgroup analyses revealed varying prognostic significances of each cytokine in different DS malignancies. Publication bias was minimal except for IL-6 in pancreatic carcinoma, affirming the robustness of most outcomes.</p><p><strong>Conclusion: </strong>Elevated circulating IL-6, CXCL, and CCL families may predict poor prognosis in certain DS, highlighting their potential as prognostic markers. Further studies are needed to translate these findings into clinical practice.</p><p><strong>Prospero registration number: </strong>CRD42022316733.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNAs in ferroptosis regulation and tumor progression of gynecological and breast cancers: molecular mechanisms and therapeutic potential.","authors":"Kiavash Hushmandi, Amir Mohammad Mirnejad, Abolfazl Bemidinezhad, Hessam Nejati, Mobin Ghaderi, Fatemeh Tavassoli Razavi, Pardis Doosti, Alireza Mafi, Mina Alimohammadi, Najma Farahani","doi":"10.1007/s12094-026-04577-1","DOIUrl":"https://doi.org/10.1007/s12094-026-04577-1","url":null,"abstract":"<p><p>Ferroptosis is a distinct form of regulated cell death that is characterized by iron-dependent oxidative damage and the excessive accumulation of lipid peroxides within cellular membranes. Increasing evidence indicates that ferroptosis is closely associated with tumor initiation, progression, metastasis, and resistance to anticancer therapies. This form of cell death has consequently attracted considerable attention as a potential therapeutic mechanism in a range of malignancies, particularly breast and gynecological cancers. Circular RNAs (circRNAs) are a diverse group of non-coding RNA molecules distinguished by their covalently closed circular structures and remarkable stability. Accumulating evidence has established circRNAs as important regulators of cancer-associated molecular processes at the post-transcriptional level. In the context of ferroptosis, circRNAs may modulate cellular susceptibility to oxidative cell death through several mechanisms, including sequestration of microRNAs, interactions with RNA-binding proteins, and regulation of signaling networks and genes involved in iron metabolism, lipid homeostasis, antioxidant defense, and redox balance. This review provides an overview of the fundamental molecular mechanisms underlying ferroptosis and examines the emerging roles of circRNAs in regulating ferroptotic responses across breast, ovarian, cervical, and endometrial cancers. Particular emphasis is placed on the molecular interactions through which circRNAs influence ferroptosis-associated pathways and on their potential utility as diagnostic, prognostic, and therapeutic biomarkers. The interplay between circRNAs and ferroptosis represents an important area of cancer research, because it may provide new insights into tumor biology and reveal previously unexplored opportunities for precision therapeutic intervention. Nevertheless, further mechanistic investigations, comprehensive in vivo studies, and well-designed clinical investigations are required to establish the translational relevance of these findings and determine whether circRNA-ferroptosis regulatory networks can be effectively exploited in clinical oncology.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world evolution of first-line ALK-positive NSCLC management in Spain.","authors":"Virginia Calvo, Jon Zugazagoitia, Elisabet García, Gerardo Villa, Antonio José Montes","doi":"10.1007/s12094-026-04582-4","DOIUrl":"https://doi.org/10.1007/s12094-026-04582-4","url":null,"abstract":"<p><strong>Objective: </strong>To describe real-world management of patients with ALK-positive advanced or metastatic NSCLC receiving first-line therapy in Spain, and to assess shifts in treatment patterns following the pricing and reimbursement of lorlatinib for first-line treatment in Spain.</p><p><strong>Methods: </strong>This retrospective, cross-sectional analysis used data from the IQVIA Oncology Dynamics™ database. Patients with ALK-positive advanced or metastatic NSCLC receiving first-line treatment in Spain were included in two cohorts: before (July 2021-June 2022) and after (July 2024-June 2025) lorlatinib introduction. Patient characteristics, molecular profiles, and treatment patterns were described using descriptive statistics.</p><p><strong>Results: </strong>A total of 342 patients were included. Patient characteristics were generally comparable across cohorts, although a higher disease burden and increased frequency of brain metastases were observed over time. A marked shift in treatment patterns was reported, with lorlatinib use increasing from 2 to 46% and becoming the most frequently prescribed first-line therapy in the later cohort, while alectinib use decreased from 85 to 41%. Among newly treated patients, lorlatinib accounted for 67% of prescriptions in the later cohort. Uptake of next-generation sequencing for molecular testing increased, and radiotherapy use declined over time.</p><p><strong>Conclusions: </strong>The management of ALK-positive NSCLC in Spain has evolved following the pricing and reimbursement of lorlatinib for first-line treatment in Spain, with changes in treatment selection and molecular testing practices observed in routine clinical settings.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149118039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGFR exon 20-altered NSCLC in China: molecular heterogeneity and real-world outcomes with sunvozertinib.","authors":"Jiahui Zhang, Yuechen Cui, Qing Ren, Xinyi Wu, Jingjing Li, Xin Liu, Bin Zhang, Dongsheng Yue","doi":"10.1007/s12094-026-04583-3","DOIUrl":"https://doi.org/10.1007/s12094-026-04583-3","url":null,"abstract":"<p><strong>Purpose: </strong>EGFR exon 20 alterations are uncommon and heterogeneous in non-small cell lung cancer (NSCLC), with reduced sensitivity to conventional EGFR tyrosine kinase inhibitors. This study aimed to characterize their molecular spectrum, clinical relevance, and real-world outcomes.</p><p><strong>Patients and methods: </strong>We retrospectively analyzed 50 patients with NSCLC harboring EGFR exon 20 alterations confirmed by next-generation sequencing. Mutation spectrum, structural distribution, co-occurring genomic alterations, clinicopathological features, treatment patterns, and overall survival (OS) were evaluated. Associations between molecular features, sunvozertinib exposure, and OS were assessed using Kaplan-Meier survival analysis and Firth penalized Cox regression.</p><p><strong>Results: </strong>EGFR exon 20 alterations showed marked molecular heterogeneity, with multiple mutation subtypes and structural subclasses. Co-occurring genomic alterations were frequent, and TP53 was the most common concomitant alteration. TP53 co-mutation was associated with inferior OS. Exploratory Kaplan-Meier analysis suggested shorter OS for far-loop than near-loop variants, although the subgroups were small and imbalanced. Among non-surgical patients, sunvozertinib exposure was associated with longer OS in unadjusted analysis, but this association did not remain statistically significant after multivariable adjustment.</p><p><strong>Conclusion: </strong>This study provides real-world evidence of the molecular and clinical heterogeneity of EGFR exon 20-altered NSCLC. TP53 co-mutation was associated with poorer OS. Exploratory analyses suggested a possible survival difference according to loop location and a potentially favorable association between sunvozertinib exposure and OS among non-surgical patients, although the adjusted results varied across models and were limited by the small number of survival events. These findings highlight the potential relevance of molecular stratification but require validation in larger prospective cohorts.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149118045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphological and molecular characterization of epithelial ovarian cancer: SEOM-SEAP consensus guidelines for biomarker integration in clinical practice.","authors":"Gabriel Matheu, María José Bermejo-Peréz, Nuria Escudero-García, Carmen Garcia-Duran, Sonia Gatius-Caldero, Eva Guerra-Alía, Susana López-Agullo, Ignacio Romero, Geanella Yange, Maria-Pilar Barretina-Ginesta","doi":"10.1007/s12094-026-04335-3","DOIUrl":"10.1007/s12094-026-04335-3","url":null,"abstract":"<p><p>Epithelial ovarian cancer (OC) is the second leading cause of death among gynecologic malignancies and exhibits marked histological and molecular heterogeneity. Advances in tumor biology and targeted therapies have increased the need for accurate biomarker characterization. This updated consensus by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) reviews key morphological and molecular features for diagnosis and providing recommendations for biomarker assessment across major OC subtypes. The document addresses classical serum biomarkers, prognostic tools, and genomic alterations with therapeutic implications, including homologous recombination deficiency (HRD), BRCA1 and BRCA2 mutations, mismatch repair status, as well as other established and emerging biomarkers. Emphasis is placed on optimal sample selection, validated techniques, and multidisciplinary integration is required to ensure diagnostic quality. These recommendations aim to optimize prognostic stratification and guide personalized treatment strategies, ultimately improving clinical outcomes in ovarian cancer.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4359-4375"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147876598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence-steered medicine in oncology: network-aware micro-combinations that safeguard standard of care and potentially improve benefit-risk.","authors":"Konstantin Gurbanov","doi":"10.1007/s12094-026-04354-0","DOIUrl":"10.1007/s12094-026-04354-0","url":null,"abstract":"<p><p>Standard oncology regimens often follow a dose-optimization paradigm: intensify a single agent until efficacy emerges or toxicity intervenes. Yet many targets sit in compensatory tumor-host networks that reroute around pathway pressure, while incremental efficacy may plateau as dose rises and toxicity escalates. Clinical reality is further complicated by heterogeneous patient states, including suppressed antigen presentation (e.g., β2-microglobulin loss or antigen-processing/presentation machinery defects), immature or poorly trafficking dendritic cells, and symptom/toxicity burdens that drive dose delays or reductions and erode relative dose intensity. These factors contribute to late-stage monotherapy failures and leave clinicians with a binary choice-more of the same therapy or a complete stop-when the actionable question is often whether a small, precisely timed change could restore the preconditions under which standard-of-care (SoC) therapy works best. Evidence-steered medicine (ESM) proposes a conservative adjunctive framework that adds only tiny, single-pulse exposures (\"micro-adjuncts\") without delaying or displacing SoC. Each micro-adjunct is pre-specified with a directional mechanistic hypothesis and read out by short-horizon proxies at 48-96 h (e.g., HLA-ABC and TAP1/2 for antigen presentation; CD86/CCR7 for antigen-presenting-cell activation and trafficking readiness; hs-CRP for systemic inflammatory tone; HRV and symptom scores for host readiness). ESM enforces three safety-first gates: a mechanistic sign-consistency check; a transportability/overlap screen to avoid out-of-support exposure; and a banded decision rule that acts only when the pessimistic bound of the expected proxy effect exceeds a preset threshold under strict exposure caps, otherwise defaulting to NO-STEP. Governance features-drug-drug interaction matrices, order-set blocks, one-click rollback, and degrade-to-rules when calibration drifts-aim to convert combination experimentation into an auditable, risk-minimizing bedside layer. This review synthesizes the rationale for micro-dosed, order-aware adjuncts, summarizes implementable class-level candidates using approved agents and routine assays (with investigational items restricted to protocol settings), and outlines an evaluation plan embedded in care that prioritizes feasibility, safety, and mechanistic informativeness while protecting SoC delivery.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4461-4468"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the MDM2/p53 axis in regulating cisplatin response in tumor cells.","authors":"Yasamin Rajabloo, Iman Akhlaghipour, Negin Taghehchian, Meysam Moghbeli","doi":"10.1007/s12094-026-04389-3","DOIUrl":"10.1007/s12094-026-04389-3","url":null,"abstract":"<p><p>Cisplatin remains a cornerstone chemotherapeutic agent for a broad spectrum of solid malignancies; however, the emergence of intrinsic and acquired resistance severely limits its clinical efficacy. Central to the cellular decision between DNA damage repair and apoptosis following cisplatin exposure is the tumor suppressor p53, whose function is tightly governed by its primary negative regulator, Murine Double Minute 2 (MDM2). This review provides a critical synthesis of the molecular interplay within the MDM2/p53 axis and its direct impact on cisplatin sensitivity. We discussed how deregulation of this axis via TP53 mutational inactivation or MDM2 overexpression enables tumor cells to tolerate cisplatin-induced genotoxic stress. Specifically, we analyzed the dual role of MDM2: its E3 ubiquitin ligase activity that targets p53 for proteasomal degradation, and its emerging p53-independent functions in promoting DNA repair fidelity. Furthermore, we evaluated the therapeutic implications of targeting this pathway with small-molecule MDM2 antagonists. We assessed preclinical and clinical evidence supporting the use of MDM2 inhibition to lower the apoptotic threshold and re-sensitize resistant tumors to cisplatin. Therefore, an understanding of the MDM2/p53 feedback loop is essential for optimizing cisplatin-based regimens and developing rational combination therapies to circumvent chemoresistance.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4597-4609"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147976941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}