Translational Oncology最新文献

{"title":"Development of multiple cell death pattern features to predict prognosis and drug sensitivity in gastric adenocarcinoma","authors":"Zhenyu Yang ,&nbsp;Haoran Li ,&nbsp;Xi’e Hu ,&nbsp;Shuai Zhou,&nbsp;Xianli He","doi":"10.1016/j.tranon.2025.102584","DOIUrl":"10.1016/j.tranon.2025.102584","url":null,"abstract":"<div><h3>Background</h3><div>Regulated cell death (RCD) pathways play a crucial role in stomach adenocarcinoma (STAD), influencing apoptosis and potentially offering new therapeutic opportunities. This study aimed to analyze the immune microenvironment, mutation landscape, and develop a prognostic framework based on RCD-related gene expression for personalized treatment in STAD.</div></div><div><h3>Methods</h3><div>Datasets from TCGA and GEO (GSE84426) were used. RCD-related genes were analyzed for differential expression with the \"limma\" R package, and unsupervised clustering was performed using \"ConsensusClusterPlus.\" Immune infiltration was assessed via ssGSEA, and pathway variations were examined with GSVA. A risk-scoring system was developed using Cox regression. Prognostic accuracy was validated through ROC curves, C-index, and multivariate analyses. Drug sensitivity was predicted using the \"oncoPredict\" package with GDSC pharmacogenomic data.</div></div><div><h3>Results</h3><div>Twenty-six RCD-associated genes showed significant prognostic relevance. Two clusters were identified, with cluster B demonstrating better overall survival. The prognostic signature, PCD Score, identified CTSV, GCSH, LZTS1, SERPINE1 as unfavorable, and DDIAS, TRAF2 as protective. Validation of the model showed strong predictive power. Functional enrichment analysis revealed key pathways like vascular smooth muscle contraction and dilated cardiomyopathy. Immune profiling revealed elevated immune activity in low-risk patients, consistent with patterns associated with immune checkpoint blockade responsiveness. Computational drug screening suggested a potential susceptibility to temozolomide in high-risk patients, offering a testable hypothesis for future research.</div></div><div><h3>Conclusion</h3><div>This study presents a robust prognostic model based on RCD-related genes, offering insights into immune response and drug sensitivity for personalized STAD treatment.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102584"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459822","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":"Drug-tolerant persister cells in head and neck squamous cell carcinoma: Molecular mechanisms and therapeutic opportunities","authors":"Hang Huong Ling ,&nbsp;Huei-Yu Huang ,&nbsp;Chih-Ming Huang ,&nbsp;Muhammad Yasir ,&nbsp;Chun-Chen Ko ,&nbsp;Vijesh Kumar Yadav ,&nbsp;Kuang-Tai Kuo ,&nbsp;Chi-Tai Yeh ,&nbsp;Jo-Ting Tsai","doi":"10.1016/j.tranon.2025.102579","DOIUrl":"10.1016/j.tranon.2025.102579","url":null,"abstract":"<div><div>Although treatments for HNSCC have improved, the cancer is still challenging because many patients tend to develop the disease again nearby and often have poor recovery. Since drug-tolerant persister (DTP) cells display a wide range of types and unique genetic characteristics, nonhormonal endocrine therapies, including chemotherapy, targeted therapy and immunotherapy, are ineffective in eliminating these cells. DTP cells evade elimination by entering a reversible dormant state characterized by altered metabolism, enhanced DNA repair capacity, and modified immune escape mechanisms, all of which promote the cells’ survival and treatment failure. Platinum-based chemotherapy, widely prescribed for HNSCC, reduces tumor size but fails to confer long-term benefits because of the strong treatment resistance of DTP cells. These cells also exhibit resistance to tyrosine kinase inhibitors by activating alternative signaling pathways. Alternative survival pathways are also activated in DTP cells when targeted therapies such as those using epidermal growth factor receptor inhibitors are used. Although programmed death 1/programmed death ligand 1 inhibitors are exciting new treatments, their effect is hampered by DTP cells that affect the immune system. This review examines the ways DTP cells make HNSCC tumor cells resistant to treatment by looking at metabolic reprogramming, DNA methylation alterations and the microenvironment of the tumor. This review further explores strategies for targeting metabolic dependencies, inhibiting DNA repair, and combining therapeutic approaches, all of which can mitigate DTP cell-mediated recurrence. Advancing strategies that specifically target DTP cells could enhance HNSCC management by reducing recurrence and improving overall prognosis.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102579"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410255","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":"B2M regulates ELANE in pyroptosis to affect pancreatic cancer progression","authors":"Hui xie ,&nbsp;Xiaonan Hu ,&nbsp;Yongde Cai ,&nbsp;Sheng Zhu ,&nbsp;Zuliang Deng","doi":"10.1016/j.tranon.2025.102613","DOIUrl":"10.1016/j.tranon.2025.102613","url":null,"abstract":"<div><div>The role of pyroptosis in pancreatic cancer remains controversial. Using two-sample Mendelian randomization (MR) integrating GWAS data from FinnGen (314,193 controls, 731 cases), pQTL data from Iceland, and the UK Biobank, we systematically investigated causal links between pyroptosis genes and pancreatic cancer. We found that Beta-2-microglobulin (<em>B2M</em>) indirectly increases pancreatic cancer risk by upregulating Neutrophil Elastase (<em>ELANE</em>)—to our knowledge, this is the first study to establish a causal, mediation-based genetic link between <em>B2M</em> and <em>ELANE</em> in the context of pancreatic cancer. Mediation analysis revealed <em>ELANE</em> accounts for 20.572 % [15.32%–25.81 %] of this effect. Sensitivity analyses confirmed robustness without significant pleiotropy, and bioinformatics validation supported our MR findings. Drug sensitivity analysis further identified potential therapeutic agents. The findings support <em>B2M</em> as a diagnostic biomarker for pancreatic cancer, given its significant overexpression in tumors and high diagnostic accuracy (AUC = 0.976, 95 % CI: 0.958–0.993), and highlight the <em>B2M</em>–<em>ELANE</em> axis—identified through a data-driven MR mediation framework—as a promising therapeutic target.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102613"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145579557","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":"Poly-ADP-ribosylation modulated by poly(ADP-ribose) polymerase 1 is associated with glucose metabolism in colorectal cancer cells","authors":"Chenxuan Zhang ,&nbsp;Peng Wang ,&nbsp;Jia Yu ,&nbsp;Jianhui Yuan ,&nbsp;Lilong Zhang ,&nbsp;Man Li","doi":"10.1016/j.tranon.2025.102623","DOIUrl":"10.1016/j.tranon.2025.102623","url":null,"abstract":"<div><div>The preference of cancer cells to generate energy from glycolysis for rapid cell proliferation is called the Warburg effect. Poly(ADP-ribose) polymerase 1 (PARP1) performs various cellular functions, including poly-ADP-ribosylation and DNA repair. In the present study, we investigated the novel effects and mechanisms of PARP1 inhibition on glucose metabolism in colorectal cancer cells under hypoxia. We subjected Caco-2 and LoVo cancer cell lines to a concentration gradient of PARP1 inhibitor in a hypoxic environment induced with a tri-gas incubator (5 % CO₂, 1 % O₂, 94 % N₂). Inhibiting PARP1 activation attenuated Poly-ADP-ribosylation, increasing the NAD⁺/NADH ratio. High concentrations of PARP1 significantly reduced the glucose consumption rate of the treated cells, while PARP1 inhibition depressed cell progression in a concentration-dependent manner. The expression of hypoxia-inducible factor-1α (HIF-1α), hexokinase 2 (HK2), and glucose transporter 1 (GLUT-1), critical for the Warburg effect and glucose metabolism, was considerably reduced after the inhibitor treatments. Moreover, inhibiting PARP1 activation reduced phosphorylated AKT (p-AKT) and mTOR (p-mTOR) levels. In conclusion, our study revealed that PARP1 inhibition decelerates the Warburg effect in colorectal cancer cells, likely through the AKT/mTOR/HIF-1α pathway.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102623"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678790","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":"The PI3K pathway is a downstream effector of NRF2 activation in the esophagus","authors":"Boopathi Subramaniyan ,&nbsp;Yahui Li ,&nbsp;Zhaohui Xiong ,&nbsp;Chorlada Paiboonrungruang ,&nbsp;Candice Bui-Linh ,&nbsp;Francis Spitz ,&nbsp;Xiaoxin Chen","doi":"10.1016/j.tranon.2025.102629","DOIUrl":"10.1016/j.tranon.2025.102629","url":null,"abstract":"<div><div>Mutations in nuclear factor erythroid 2–related factor 2 (<em>NFE2L2</em> or <em>NRF2</em>) occur in 10–22 % of esophageal squamous cell carcinoma (ESCC) cases and result in NRF2 activation, promoting tumor progression, and therapeutic resistance. Although previous studies suggested a link between NRF2 and kinases, specific kinases responsive to NRF2 activation remain to be fully identified. Using protein phosphorylation profiling and kinase activity profiling, we identified phosphatidylinositol 3-kinase (PI3K) pathway as a downstream effector in NRF2^W24C-KYSE70 cells compared to isogenic NRF2^null-KYSE70 cells. AREG, pEGFR, PIK3CA, pAKT, p-S6, and p-PTEN were downregulated in NRF2 deficient cells. Notably, NRF2 deficiency sensitized ESCC cells to EGFR, PIK3CA, and AKT inhibitors. Co-treatment with Alpelisib (a PIK3CA inhibitor) and Pyrimethamine (an NRF2 inhibitor) synergistically suppressed the growth of NRF2^W24C-KYSE70 and NRF2^D77V-KYSE180 cells. <em>In vivo</em>, NRF2 activation in the esophageal epithelium of <em>Keap1^-/-</em> and <em>Sox2CreER;LSL-Nrf2^E79Q/+</em> mice resulted in upregulation of pAKT, p-mTOR, and pS6. In human ESCC tissues, expression of pNRF2 (an active form of NRF2) was positively associated with that of pAKT and p-mTOR. Furthermore, co-treatment with Pyrimethamine and Alpelisib significantly inhibited hyperproliferation and hyperkeratinization in the esophageal epithelium of <em>Sox2CreER;LSL-Nrf2^E79Q/+</em>mice. Together, our data demonstrates the PI3K pathway as a downstream effector of NRF2 activation in the esophagus, and co-targeting of NRF2 and the PI3K pathway may offer a promising therapeutic strategy for NRF2^Mut ESCC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102629"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678825","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":"Biomarker analysis from a Phase 1/1b study of tusamitamab ravtansine in patients with advanced non-small cell lung cancer","authors":"Anas Gazzah ,&nbsp;Nils Ternès ,&nbsp;Joon Sang Lee ,&nbsp;Emma Wang ,&nbsp;Dimitri Carene ,&nbsp;Hong Wang ,&nbsp;Nina Masson ,&nbsp;Eric Boitier ,&nbsp;Aude Lartigau ,&nbsp;Nathalie Mace ,&nbsp;Mustapha Chadjaa ,&nbsp;Colette Dib ,&nbsp;Manoel Nunes ,&nbsp;Gaëlle Muzard ,&nbsp;Sandrine Longuemaux-Valence ,&nbsp;Anne-Laure Bauchet","doi":"10.1016/j.tranon.2025.102615","DOIUrl":"10.1016/j.tranon.2025.102615","url":null,"abstract":"<div><h3>Background</h3><div>Tusamitamab ravtansine demonstrated antitumor activity in the Phase 1/1b study of advanced non-squamous non-small cell lung cancer with high (HE, ≥2+ intensity in ≥50 % of tumor cells) or moderate (ME, ≥2+ intensity in ≥1 % to &lt;50 % of tumor cells) carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expression. Tumor CEACAM5 expression, biomarker associations and whether biomarkers predict objective response rate (ORR) were explored.</div></div><div><h3>Methods</h3><div>We assessed CEACAM5, circulating CEACAM5 (cCEACAM5) and CEA (cCEA). Enrollment was according to immunohistochemistry (IHC) CEACAM5 membrane expression: HE (<em>n</em>=64) and ME (<em>n</em>=28). Patients received tusamitamab ravtansine 100 mg/m² intravenously every 2 weeks.</div></div><div><h3>Results</h3><div>cCEA and cCEACAM5 were strongly associated (Spearman ρ, 0.99), with moderate associations between IHC CEACAM5 and cCEA or cCEACAM5 (Spearman ρ, 0.43 and 0.38). In patients with baseline cCEA data, 40.3 % (25/62) of HE and 25 % (7/28) of ME had cCEA ≥100 µg/L (median: 71.6 µg/L [1–8809] versus 12.4 µg/L [0.5–684]). Among response-evaluable patients in HE, ORR for high cCEA (≥100 µg/L) was 41.7 % (10/24) versus 8.1 % (3/37) for low cCEA, and in ME, ORR was 0/7 versus 10 % (2/20). Elevated CEACAM5 mRNA was observed in HE versus ME (<em>P</em> = 0.0027). <em>EGFR</em> and <em>KRAS</em> alterations were present in 44.8 % and 65.5 % of HE and in 21.4 % and 78.6 % of ME patients, respectively.</div></div><div><h3>Conclusions</h3><div>In CEACAM5 HE, the ORR was greater with high versus low cCEA. Associations were observed between cCEA and cCEACAM5; IHC CEACAM5, cCEA, and cCEACAM5; IHC CEACAM5 and CEACAM5 mRNA, but not between IHC CEACAM5 and oncogenic drivers.</div><div><strong>Clinical Trial Registration:</strong> NCT02187848</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102615"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669782","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":"Unveiling shared PANoptosis mechanisms in LUAD and osteoarthritis via bioinformatics and machine learning","authors":"Hailin Xiong ,&nbsp;Junjie Liu ,&nbsp;Shuyi Zhang ,&nbsp;Xuli Guo","doi":"10.1016/j.tranon.2025.102586","DOIUrl":"10.1016/j.tranon.2025.102586","url":null,"abstract":"<div><div>Lung adenocarcinoma (LUAD) and osteoarthritis (OA) pose significant therapeutic challenges due to their invasive heterogeneity and limited treatment options. This study investigates PANoptosis-related genes in LUAD and OA to develop a prognostic risk model using bioinformatics and machine learning. We obtained gene expression data from TCGA, GEO, and MSigDB, then applied consensus clustering to stratify LUAD samples and identified PANoptosis-associated differentially expressed genes (DEGs). For OA, ssGSEA and WGCNA were used to pinpoint hub genes linked to PANoptosis. Functional enrichment analyses (GO/KEGG) revealed key pathways in both diseases. By intersecting LUAD DEGs and OA hub genes, we refined candidate genes using LASSO and Random Forest algorithms, ultimately selecting five key genes (S100A3, PFN2, DEFB1, TSPO, and KMO) for model construction. The prognostic model demonstrated robust predictive performance. Additionally, immune infiltration and mutational profiling in LUAD provided mechanistic insights for potential therapeutic strategies. Our findings highlight shared PANoptosis-related pathways in LUAD and OA, offering a novel framework for risk stratification and targeted therapy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102586"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145475404","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":"Clinical and molecular variations in Burkitt lymphoma","authors":"Eoghan O’Connor ,&nbsp;Patricia Scanlan ,&nbsp;Owen Patrick Smith ,&nbsp;Melinda Halasz","doi":"10.1016/j.tranon.2025.102611","DOIUrl":"10.1016/j.tranon.2025.102611","url":null,"abstract":"<div><div>Burkitt lymphoma (BL) is an aggressive B-cell non-Hodgkin lymphoma, historically classified into three subtypes; endemic, sporadic and immunodeficiency associated BL. Accumulating evidence suggests that Epstein-Barr virus (EBV)-positive and EBV-negative BL represent biologically distinct entities. In this review, we aim to compare the clinicopathological and molecular differences in BL in the context of EBV status and chronic malaria infection.</div><div>From our review, clinical features of BL vary by both EBV status and geographical region, reflecting underlying epidemiological differences. The cell of origin may also differ between EBV-positive and EBV-negative cases. At a molecular level, differences based on EBV status include variations in the immunoglobulin (<em>IG</em>)::<em>MYC</em> translocation breakpoints, mutations in the inhibitor of DNA binding 3 (<em>ID3</em>)/ transcription factor 3 (<em>TCF3</em>)/ cyclin D3 (<em>CCND3</em>) signalling axis, the anti-apoptotic effects of EBV latency gene products, differences in the alternative reading frame (ARF)/ mouse double minute 2 (MDM2)/p53 and ataxia-telangiectasia mutated (ATM)/ ATM and RAD3-related (ATR) pathways, and deregulation of B-cell leukemia/lymphoma 2 (BCL-2) family proteins. We further discuss the theory that aberrant activation-induced cytidine deaminase (AID) expression, in the setting of EBV infection and chronic malaria exposure, is the most likely aetiology of endemic BL.</div><div>This review provides a comprehensive summary of key molecular differences between EBV-positive and EBV-negative BL, that may guide the development of future targeted therapeutic strategies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102611"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623612","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":"HERC4 downregulates KRT19 to promote lung adenocarcinoma, migration, invasion and EMT","authors":"Hao-Jia Sun ,&nbsp;Ming-Hui Peng ,&nbsp;Zi-Yang Feng ,&nbsp;Hua Fu ,&nbsp;Xue-Wen Liu","doi":"10.1016/j.tranon.2025.102593","DOIUrl":"10.1016/j.tranon.2025.102593","url":null,"abstract":"<div><h3>Background</h3><div>Metastasis is a major cause of treatment failure and poor prognosis in lung adenocarcinoma (LUAD). Epithelial-mesenchymal transition (EMT) plays a crucial role in promoting LUAD metastasis. Pulmonary sarcomatoid carcinoma (PSC), a highly aggressive non-small cell lung cancer subtype, contains both carcinomatous component (CaC) and sarcomatous component (SaC) with strong metastatic potential. Previous studies have shown that EMT contributes to the formation of Sac in PSC.</div></div><div><h3>Methods</h3><div>The differential expression of KRT19 between SaC and CaC in PSC was screened and validated using immunohistochemistry. GO, KEGG analysis were conducted to investigate the potential mechanism of KRT19. The CCK-8, wound healing, transwell assay and mouse model were used to confirm the impact of KRT19 on cell proliferation, migration and invasion in LUAD. The upstream regulatory molecules of KRT19 were identified and validated through CO-IP, GST Pull-down Assay and ubiquitination experiments.</div></div><div><h3>Results</h3><div>KRT19 was found to be downregulated in SaC compared to CaC and LUAD. Knock down of KRT19 in A549 and PC-9 cells led to EMT, decreased adhesion, and increased proliferation and metastasis. HERC4 was identified as a potential upstream regulator of KRT19, with its expression negatively correlated with KRT19 levels. HERC4 promoted KRT19 ubiquitination, leading to its downregulation.</div></div><div><h3>Conclusion</h3><div>KRT19 downregulation promoted LUAD cell EMT, enhancing metastatic potential. HERC4 functioned as an upstream regulator that suppresses KRT19 expression by promoting its ubiquitination.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102593"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145453156","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":"Integrative multi-omics of matched primary and liver metastatic colorectal cancer organoids identifies putative molecular targets","authors":"Chae-Young Kim ,&nbsp;Soon-Chan Kim ,&nbsp;Rumi Shin ,&nbsp;Min Jung Kim ,&nbsp;Seung-Yong Jeong ,&nbsp;Ji Won Park ,&nbsp;Ja-Lok Ku","doi":"10.1016/j.tranon.2025.102592","DOIUrl":"10.1016/j.tranon.2025.102592","url":null,"abstract":"<div><div>Hepatic metastasis from colorectal cancer (CRC) mainly accounts for the dismal prognosis of advanced CRC. Metastasized tumor cells exhibit strong resistance to commonly used systemic chemotherapy, which causes the high mortality of colorectal liver metastasis (CLM) patients. Although previous studies using biological resources have suggested multiple metastatic factors, molecular integration into chemotherapeutic responses is seldom studied.</div><div>In this study, we established five pairs of CLM organoids, which were subjected to a multi-omics approach including genetic, transcriptional, exosomal miRNA and pharmacological analyses. These multi-omics layers were interlinked through machine learning analysis to construct a drug response prediction model.</div><div>Our approach not only recapitulated druggable molecular targets that were specifically dysregulated in LM organoids but also potentially revealed a statistical connection to systemic therapy regimens.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102592"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145453247","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}