Translational Oncology最新文献

{"title":"Ferroptosis induction enhances anti-PD-1 efficacy in NSCLC via HIF-1α/PD-L1 modulation","authors":"Zimin Wang ,&nbsp;Hao Liu ,&nbsp;Jiawei Liang ,&nbsp;Ying Zhang ,&nbsp;William C. Cho ,&nbsp;Minhua Ye ,&nbsp;Dehua Ma ,&nbsp;Min Kong ,&nbsp;Chengchu Zhu ,&nbsp;Jianfei Shen","doi":"10.1016/j.tranon.2026.102685","DOIUrl":"10.1016/j.tranon.2026.102685","url":null,"abstract":"<div><h3>Background</h3><div>The monotherapeutic efficacy of immune checkpoint inhibitors (ICIs) remains unsatisfactory in patients suffering from non-small-cell lung cancer (NSCLC). Ferroptosis, an iron-dependent cell death process, has been identified as a promising immunotherapy adjuvant; however, ferroptosis inducers (such as erastin, RSL3) may paradoxically up-regulate hypoxia-inducible factor 1α (HIF-1α) and programmed death ligand 1 (PD-L1) to propel tumor immune evasion. It is critical to explore the molecular mechanism of ferroptosis in NSCLC immunotherapy and verify the efficacy of combined regimens for overcoming ICI limitations clinically.</div></div><div><h3>Methods</h3><div>This work analyzed 162 NSCLC patients receiving immunotherapy retrospectively to evaluate correlation between PD-L1 expression and progression-free survival (PFS). In vitro, CCK-8 assay, flow cytometry, qPCR, and Western blotting were utilized to measure impacts of ferroptosis inducers (Erastin, RSL3) upon cell viability, reactive oxygen species (ROS) levels, and PD-L1/HIF-1α expression in A549/H1299 NSCLC cells; ferroptosis-specific effects were validated by means of iron chelators (DFO, ferrostatin-1). In vivo, subcutaneous tumor models were built in C57BL/6 mice with LLC cells; therapeutic effects of ferroptosis inducer (IKE) alone or combined with anti-PD-1 antibody were evaluated through tumor weight measurement and immunohistochemistry (IHC). HIF-1α binding to PD-L1 promoter was confirmed via chromatin immunoprecipitation (ChIP); related signaling pathways were explored using transcriptome sequencing and KEGG enrichment analysis.</div></div><div><h3>Results</h3><div>For NSCLC patients who received immunotherapy, high PD-L1 expression correlated with longer PFS, and 4-HNE was associated positively with PD-L1 and CD8⁺T infiltration. In vitro, Erastin/RSL3 induced dose-dependent cell death, ROS accumulation, and PD-L1 up-regulation, reversed by iron chelators. In vivo, IKE+anti-PD-1 inhibited tumor growth significantly, whereas it increased CD8⁺T infiltration. Mechanistically, Erastin up-regulated HIF-1α via PI3K-AKT, which bound PD-L1 promoter (ChIP-verified), reversed by iron chelators.</div></div><div><h3>Conclusions</h3><div>Ferroptosis inducers have dual effects in NSCLC, namely, promoting tumor cell death and triggering PD-L1-dependent immune evasion via the PI3K-AKT-HIF-1α pathway. However, combining ferroptosis inducers with anti-PD-1 antibodies retains the anti-tumor effect of ferroptosis and overcomes immune evasion by obstructing the PD-L1 pathway, offering a novel strategy for enhancing NSCLC immunotherapy efficacy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102685"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NPM1c⁺-driven lncRNA dysregulation in AML: Mechanisms, Controversies and translational roadblocks","authors":"Qiang Zhang ,&nbsp;Yu Fu ,&nbsp;Jihong Zhang","doi":"10.1016/j.tranon.2026.102683","DOIUrl":"10.1016/j.tranon.2026.102683","url":null,"abstract":"<div><div>In the landscape of acute myeloid leukemia (AML) research, mutations in nucleophosmin 1 (<em>NPM1</em>) are the most prevalent genetic alterations. The leukemogenic mutant variant, <em>NPM1c⁺</em>, is associated with a distinct gene expression profile linked to leukemia, but the downstream oncogenic pathways remain only partially understood. Long non-coding RNAs (lncRNAs) are RNA molecules with known regulatory roles in human development and disease. Research implicates many lncRNAs in hematopoiesis and leukemogenesis, revealing correlations between their expression and clinical parameters in AML patients. While <em>NPM1c⁺</em> AML exhibits a distinct lncRNA signature, it remains contentious whether these molecules are bona fide drivers or passenger events, and how their context-dependent functions can be therapeutically exploited.</div><div>This review focuses on lncRNAs in <em>NPM1c⁺</em> AML, highlighting their roles in pathogenesis, prognosis, and chemoresistance. By systematically elucidating the role of lncRNAs as pivotal factors in the diagnosis, treatment, and prognosis of <em>NPM1c⁺</em> AML, this study addresses a gap in the existing literature. Our analysis of specific lncRNAs, such as HOTAIRM1, HOXB-AS3, CRNDE, HOXBLINC, LONA, IFEX9, XLOC_109948, and HOTTIP, enhances our understanding of the molecular mechanisms underlying AML in the context of <em>NPM1c⁺</em>. These findings lay the groundwork for developing targeted therapies and improved prognostic tools for <em>NPM1c⁺</em>AML.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102683"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial and single-cell multi-omics reveal pro-angiogenic THY1⁺ fibroblast subtypes predicting prognosis in prostate cancer","authors":"Yongqiang Huang ,&nbsp;Chunping Xiang ,&nbsp;Yu Wang ,&nbsp;Wei Zhang ,&nbsp;Leilei Du ,&nbsp;Wenfeng Wang ,&nbsp;Guohai Shi ,&nbsp;Jianhua Wang","doi":"10.1016/j.tranon.2026.102664","DOIUrl":"10.1016/j.tranon.2026.102664","url":null,"abstract":"<div><h3>Background</h3><div>Cancer-associated fibroblasts (CAFs) play a key role in prostate cancer (PCa) progression, though their heterogeneity and specific protumorigenic subsets remain poorly characterized. This study aimed to identify and validate a distinct <em>THY1</em>⁺ CAF subset associated with aggressive PCa.</div></div><div><h3>Methods</h3><div>Multiomics data from public (TCGA-PRAD, GEO) and prospective (FUSCC, <em>n</em> = 84) cohorts were analyzed. An 8-gene CAF-derived prognostic signature was constructed using LASSO Cox regression. <em>THY1</em>⁺ CAF clusters were identified via scRNA-seq. Primary CAFs were isolated from patient tissues, and <em>THY1</em>⁺/<em>THY1</em>⁻ subpopulations were purified via MACS/FACS. Angiogenic function and secretory profiles were assessed through tube formation assays, ELISA, and antibody arrays. <em>THY1</em> knockdown and CXCR2 inhibition were used for mechanistic studies. Clinical relevance was evaluated via qPCR and multiplex immunohistochemistry on tissue microarrays.</div></div><div><h3>Results</h3><div>High CAF abundance correlated with aggressive clinicopathological features and poor prognosis in PCa. The 8-gene signature effectively predicted biochemical recurrence (BCR). scRNA-seq revealed <em>THY1</em>⁺ CAFs as a proangiogenic subpopulation. <em>THY1</em>⁺ CAFs enhanced angiogenesis via increased secretion of CXCL6 and VEGFA. CXCL6 promoted endothelial tube formation through CXCR2 activation, while <em>THY1</em> knockdown downregulated VEGFA and impaired angiogenesis. High <em>THY1</em>⁺ CAF infiltration was associated with significantly worse recurrence-free survival.</div></div><div><h3>Conclusion</h3><div><em>THY1</em>⁺ CAFs represent a proangiogenic subset that drives PCa progression via the CXCL6/CXCR2 axis and THY1-mediated VEGFA expression. These findings highlight stromal THY1 and the CXCL6/CXCR2 pathway as potential therapeutic targets.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102664"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic efficacy of blood biomarkers for differentiating early-stage pancreatic cancer from chronic pancreatitis: A systematic review and network meta-analysis","authors":"Di Wu ,&nbsp;Zeng-Kan Du ,&nbsp;Yuan-Chen Wang ,&nbsp;Yi-Zhou Zheng ,&nbsp;Hang-Ming Qi ,&nbsp;Yu-Ru-Chen Zhu ,&nbsp;Yu Cao ,&nbsp;Lei Wang ,&nbsp;Wen-Bin Zou ,&nbsp;Zhuan Liao","doi":"10.1016/j.tranon.2026.102674","DOIUrl":"10.1016/j.tranon.2026.102674","url":null,"abstract":"<div><h3>Background</h3><div>Early diagnosis of pancreatic cancer (PC) remains challenging, particularly in patients with chronic pancreatitis (CP). Currently, imaging is often inaccurate and biopsy is inherently invasive. This is the first network meta-analysis (NMA) comparing blood-based biomarkers for differentiating PC from CP.</div></div><div><h3>Methods</h3><div>PubMed and EMBASE were searched for studies evaluating blood-based biomarkers for distinguishing PC from CP. Risk of bias was assessed with QUADAS-2. We conducted individual biomarker meta-analysis with generalized bivariate models. For the NMA, we applied a Bayesian inference approach via a Markov-chain Monte Carlo random effects model. The surface under the cumulative ranking curve was used to rank the diagnostic performance of the biomarkers.</div></div><div><h3>Results</h3><div>Across 139 enrolled studies, 49 biomarkers or panels were analyzed. For differentiating PC from CP, tumor polypeptide antigen (TPA) had the highest area under the summary receiver operating characteristic curve (AUSROC) (0.92). The NMA revealed that microRNA-196b (miR-196b) ranked highest in sensitivity (OR 3.74e+27), while the combination of carbohydrate antigen 19–9 (CA199) and a panel of eight extracellular vesicle long RNAs (exLRs) exhibited the highest specificity (OR 3.78). For early-stage (stage I and II) PC, the eight exLRs showed the highest relative sensitivity (OR 7.00), and carcinoembryonic antigen (CEA) demonstrated the highest specificity (OR 4.70).</div></div><div><h3>Conclusion</h3><div>CA199 demonstrated only moderate diagnostic discrimination between PC and CP, with reduced efficacy in early-stage PC. Combining CA199 and eight exLRs exhibited promising differential diagnostic efficacy with both high sensitivity and specificity.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102674"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogenic role of talin-1 in glioma: Association with poor prognosis and regulation of the TGF-beta signaling pathway","authors":"Jiayuan Li ,&nbsp;Dongdong Zhang ,&nbsp;Huandi Zhou ,&nbsp;Liubing Hou ,&nbsp;Yu Wang ,&nbsp;Zizhou Zhang ,&nbsp;Yanqiang Wang ,&nbsp;Xiuwu Li ,&nbsp;Le Yi ,&nbsp;Xiaomin Liu ,&nbsp;Yongzhi Wang ,&nbsp;Xiaoying Xue","doi":"10.1016/j.tranon.2026.102691","DOIUrl":"10.1016/j.tranon.2026.102691","url":null,"abstract":"<div><div><em>TLN1</em>, a cytoskeletal protein associated with various tumors, remains inadequately studied in gliomas. In this study, we examined the functional role and mechanisms of <em>TLN1</em> in glioma pathogenesis. Utilizing public databases, we conducted differential expression, survival (Kaplan-Meier/ROC), and regression analyses, which were subsequently validated with institutional datasets and clinical tissues. In vitro experiments demonstrated that <em>TLN1</em> knockdown in glioma cells resulted in reduced proliferation (CCK8/EDU), migration and invasion (wound healing/Transwell), and increased apoptosis (AO/EB/flow cytometry); these findings were corroborated by Western blot analyses. Gene Set Enrichment Analysis (GSEA) linked <em>TLN1</em> to the TGF-beta signaling pathway, a connection further validated by Western blot and in vivo murine models. Both public and institutional data indicated that <em>TLN1</em> was upregulated in gliomas, with elevated expression correlating with poor prognosis. Furthermore, <em>TLN1</em> knockdown inhibited glioma growth and progression in vitro and in vivo, primarily through the TGF-beta signaling pathway. Our findings establish <em>TLN1</em> as an oncogenic driver in gliomas and highlight its potential as a therapeutic target.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102691"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NF-κB activation as a pro-survival signal from pharmacological inhibition of pyruvate dehydrogenase kinase 1 in non-small-cell lung carcinoma cell models","authors":"Quan Liu ,&nbsp;Maoxin Ran ,&nbsp;Wenying Shan ,&nbsp;Shao-Lin Zhang ,&nbsp;Kin Yip Tam","doi":"10.1016/j.tranon.2026.102681","DOIUrl":"10.1016/j.tranon.2026.102681","url":null,"abstract":"<div><div>Targeting Pyruvate dehydrogenase kinase (PDK) has emerged as one of the potential therapeutic strategies for non-small cell lung carcinoma (NSCLC). <strong>64</strong>, a recently reported PDK1 inhibitor derived from 2,2-dichloroacetophenone (DAP), exhibited promising anticancer effects in NSCLC models. Herein, we sought to investigate the mechanism of action of <strong>64</strong> in two NSCLC cell lines, namely, NCI-H1975 and NCI-H1650. We found that <strong>64</strong> induced intrinsic cancer cell apoptosis by releasing cytochrome C (CytC) from mitochondria, leading to caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage, which was mediated by reactive oxygen species (ROS). Moreover, we have shown that <strong>64</strong> induced mitochondrial membrane potential (MMP) depolarization and AMPK/MAPK activations were also ROS driven. With the aid of sequencing studies and follow-up biochemical evaluations, we found that <strong>64</strong> activated the NF-κB pathway through P38 MAPK, while the combination of P38 MAPK inhibitor <strong>SB203580</strong> with <strong>64</strong> diminished such activation. Interestingly, the combined use of <strong>64</strong> and NF-κB inhibitor (<strong>JSH-23</strong>) increased pro-apoptosis protein (Bax) expression and decreased pro-survival protein (Bcl-2) expression, resulting in enhanced cancer cell apoptosis <em>via</em> JNK pathway. Our results suggested that <strong>64</strong> induces cancer cell apoptosis in NSCLC models through ROS, while NF-κB activation serves as a survival mechanism upon PDK1 inhibition.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102681"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphoglucomutase 5 suppresses gallbladder cancer progression by inhibiting lactate-driven STAT3 signaling","authors":"Wencong Ma ,&nbsp;Cheng Zhang ,&nbsp;Anjiang Gou ,&nbsp;Mingtai Hu,&nbsp;Yao Huang,&nbsp;Xiaoqing Jiang,&nbsp;Jianyang Ao,&nbsp;Jinghan Wang","doi":"10.1016/j.tranon.2026.102678","DOIUrl":"10.1016/j.tranon.2026.102678","url":null,"abstract":"<div><div>Gallbladder cancer (GBC) is a highly aggressive malignancy of the biliary tract with limited therapeutic options. Phosphoglucomutase 5 (PGM5), a key enzyme in glucose metabolism, has been implicated as a tumor suppressor in several cancers, yet its role and mechanism in GBC remain unclear. Here, we demonstrate that PGM5 is significantly downregulated in GBC tissues, and its low expression correlates with poor prognosis. Using integrated bioinformatic analysis, we found that PGM5 loss is associated with enhanced glycolysis and activation of the STAT3 signaling pathway. Functionally, PGM5 overexpression significantly inhibited GBC cell proliferation, migration, and invasion, and promoted apoptosis, whereas PGM5 knockdown exerted the opposite effects. Mechanistically, PGM5 suppressed lactate production by downregulating lactate dehydrogenase A (LDHA), leading to decreased phosphorylation of STAT3. The anti-tumor effects of PGM5 were reversed by exogenous lactate supplementation, and the glycolytic inhibitor 2-DG abrogated the oncogenic phenotypes induced by PGM5 silencing. In a mouse xenograft model, PGM5 overexpression significantly restrained tumor growth, reduced LDHA and p-STAT3 levels, and decreased intratumoral lactate content. Our findings reveal that PGM5 acts as a tumor suppressor in GBC through disruption of the lactate-STAT3 signaling axis, highlighting its potential as a therapeutic target for metabolic intervention in GBC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102678"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An exploratory study on the relationship between renal cell carcinoma and CAFs infiltration by integrating Pathomics and collagen features","authors":"Rongjiang Wang ,&nbsp;Mengting Jiang ,&nbsp;Zhaojun Li ,&nbsp;Zhucheng Zhao ,&nbsp;Junwen Shen","doi":"10.1016/j.tranon.2026.102665","DOIUrl":"10.1016/j.tranon.2026.102665","url":null,"abstract":"<div><h3>Objective</h3><div>Cancer-associated fibroblasts (CAFs) are a critical component of the tumor microenvironment and play a significant role in renal cell carcinoma (RCC) progression and treatment response. However, current methods for evaluating CAFs infiltration in RCC are inadequate. This study aims to develop a non-invasive histopathological model based on H&amp;E staining and collagen features to predict CAFs infiltration and investigate its prognostic value and biological relevance.</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis using H&amp;E pathological images and clinical data from The Cancer Genome Atlas (TCGA) database. A Pathomics model integrating 465 histopathological features was constructed using machine learning algorithms (<em>n</em> = 354) to predict CAFs infiltration. A preliminary technical validation was performed using multiphoton microscopy-based collagen quantification (<em>n</em> = 25) to assess the correlation between the Pathomics Score and CAF-related fibrotic activity. Enrichment analysis, immune cell infiltration profiling, and mutation analysis were employed to explore the biological mechanisms underlying the model.</div></div><div><h3>Results</h3><div>The Pathomics model demonstrated high predictive accuracy (AUC=0.813) and correlated significantly with collagen deposition (<em>r</em> = 0.66, <em>P</em> &lt; 0.001). High Pathomics scores were independently associated with poor survival (HR=1.80, <em>P</em> = 0.003) and linked to key biological processes, including YAP/TAZ activation, extracellular matrix (ECM) remodeling, immune suppression (e.g., CD276, IDO1), and frequent mutations in VHL and PBRM1 (&gt;40%).</div></div><div><h3>Conclusion</h3><div>This study establishes the first H&amp;E-based Pathomics framework for quantifying CAFs infiltration in RCC, providing a cost-effective and non-invasive tool for preliminary risk stratification. The model’s strong correlation with collagen features and its ability to reveal underlying molecular mechanisms highlight its potential for potential value in understanding the stromal microenvironment, though further external validation is required for clinical translation.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102665"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances on drug therapy for KRASG12C-mutant non-small-cell lung cancer","authors":"Ting Tian,&nbsp;Wangping Li","doi":"10.1016/j.tranon.2026.102668","DOIUrl":"10.1016/j.tranon.2026.102668","url":null,"abstract":"<div><div>Lung cancer has an extremely high mortality rate among malignant tumors, posing a significant threat to human health Among all lung cancer cases, non-small cell lung cancer (NSCLC) accounts for a significant proportion and has become a hot topic in clinical research and treatment. The Kirsten rat sarcoma viral oncogene homolog (<em>KRAS</em>) is one of the most common oncogenic drivers in NSCLC, closely associated with tumor initiation, treatment response, and prognosis. However, due to the relatively smooth surface of the <em>KRAS</em> protein and the lack of drug-binding pockets, it has long been regarded as an \"undrugable target\". With further research, recently, targeted drugs targeting the <em>KRAS^G12C</em> gene mutation have achieved significant breakthroughs in clinical trials, especially the application of <em>KRAS^G12C</em>-specific inhibitors adagrasib and sotorasib, which has changed the treatment landscape for NSCLC patients. To address challenges such as tumor heterogeneity, the complexity of the tumor microenvironment, interpatient variability, and acquired drug resistance mechanisms, combination therapy strategies involving <em>KRAS^G12C</em> inhibitors have emerged sequentially. This article systematically reviews the progress of targeted therapy for <em>KRAS^G12C</em>-mutant NSCLC and the results of related clinical trials, while exploring novel therapeutic strategies for patients with <em>KRAS^G12C</em> mutations, aiming to provide a reference for the selection of clinical treatment regimens.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102668"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity and cancer: Relevance of DNA damage response","authors":"Bhavana Deshmukh ,&nbsp;Amrendra Kumar Ajay ,&nbsp;Manoj Kumar Bhat","doi":"10.1016/j.tranon.2025.102657","DOIUrl":"10.1016/j.tranon.2025.102657","url":null,"abstract":"<div><div>Obesity is a non-communicable, multifactorial disorder that has steadily emerged as one of the major global health concerns. It significantly increases the risk of diabetes, cardiovascular diseases and cancer. In obesity, the accumulation of excess fat causes increase in the circulatory levels of adipose tissue-specific hormones (adipokines) and exacerbates carbohydrate-fuelled metabolic stress. These factors promote oxidative and genotoxic stress, resulting in chronic inflammation. Moreover, obesity-related factors contribute to increase in DNA damage and disrupt the DNA Damage Response (DDR), thereby promoting genomic instability. Consequently, obesity may facilitate a complex, multi-step process of cellular transformation and cancer progression. However, the mechanisms linking obesity-associated DDR alterations to cancer progression are active areas of investigation. Therefore, elucidating these aspects of DDR in obesity could enhance our understanding of the risk assessment and facilitate advancement in treatment strategies for patients with cancers and obesity.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102657"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}