Molecular Cancer最新文献

{"title":"Smart hydrogels for overcoming cancer multidrug resistance.","authors":"Yong Wang,Baoyan Liu,Zou-Fang Huang,Harsh Patel,Jinming Yu,Man Hu,Zhe-Sheng Chen","doi":"10.1186/s12943-026-02660-3","DOIUrl":"https://doi.org/10.1186/s12943-026-02660-3","url":null,"abstract":"Multidrug resistance (MDR) remains the principal impediment to curative oncology, driven by complex interplays between cancer cells and the tumor microenvironment (TME). While nanomedicines have sought to overcome these delivery barriers, their clinical translation is often hampered by the heterogeneity of the enhanced permeability and retention (EPR) effect and by inefficient intratumoral delivery. In this review, we argue that overcoming MDR requires a transition beyond traditional passive drug delivery, advocating active, localized remodeling of the tumor ecosystem. Next-generation injectable hydrogels are increasingly recognized as localized viscoelastic niches that combine controlled intratumoral retention with the capacity to actively modulate biological responses within tumor TME. By converging principles of mechanobiology and immunometabolism, these hydrogels enable a multi-tiered strategy to dismantle multidimensional MDR. This approach begins with the biomechanical softening of the extracellular matrix to decouple mechanotransduction driven by Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), followed by the metabolic disruption of hypoxia-driven bioenergetics. Beyond the extracellular landscape, nanogel-enabled trafficking allows payloads to circumvent intracellular sequestration and efflux transporters, while immunomodulatory niches mobilize antitumor immunity through in situ vaccination and myeloid reprogramming. Finally, we evaluate the integration of artificial intelligence-driven design and patient-derived organoids as a technical bridge to reconcile laboratory ingenuity with clinical utility, aiming to transform the TME into a vulnerable therapeutic target.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"18 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KRAS and MYC synergistic inhibition: a powerful strategy targeting KRAS-mutant cancers.","authors":"Man Yan,Kai Liu,Jing Xu,Yandi Liu,Liechen Ji,Shiwu Zhang","doi":"10.1186/s12943-026-02659-w","DOIUrl":"https://doi.org/10.1186/s12943-026-02659-w","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"123 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author's Response to the Commentary by Raitoharju E et al. on \"Epigenome-wide analysis across the development span of pediatric acute lymphoblastic leukemia: backtracking to birth\".","authors":"Farah J Nassar,Vincent Cahais,Jill A McKay,Gordon Strathdee,Yong Sun Lee,Natalia Spitz,Eric Nickels,Jessica Nordlund,Richard Saffery,Terence Dwyer,Per Magnus,Monica Cheng Munthe-Kaas,Zdenko Herceg,Joseph Leo Wiemels,Akram Ghantous","doi":"10.1186/s12943-025-02494-5","DOIUrl":"https://doi.org/10.1186/s12943-025-02494-5","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"64 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary on \"Intercellular TIMP-1-CD63 signaling directs the evolution of immune escape and metastasis in KRAS-mutated pancreatic cancer cells\".","authors":"Biao Zhang, Dong Shang","doi":"10.1186/s12943-026-02656-z","DOIUrl":"10.1186/s12943-026-02656-z","url":null,"abstract":"<p><p>We recently carefully read the article titled “Intercellular TIMP-1-CD63 signaling directs the evolution of immune escape and metastasis in KRAS-mutated pancreatic cancer cells” published by Chu-An Wang et al. in Molecular Cancer. While this study provides valuable insights into tumor-immune crosstalk, we raise two points for clarification to enhance its precision. First, the manuscript classifies T2N0M0 samples as stage II pancreatic ductal adenocarcinoma (PDAC), which conflicts with the eighth edition of the AJCC Cancer Staging Manual that designates T2N0M0 as stage IB. Second, the authors used pancreatic stellate cells (PSCs) as a surrogate for fibroblasts to model stromal effects, but accumulating evidence indicates that PSCs and fibroblasts are not equivalent. To address this, we integrated single-cell, spatial, and bulk transcriptomic data from multiple cohorts. Our analyses revealed substantial differences between fibroblasts and stellate cells in abundance (fibroblasts enriched in primary pancreatic cancer tumor tissues), prognostic relevance (high fibroblasts associated with poorer survival, high stellate cells with better prognosis), spatial distribution (fibroblasts localized around malignant tumor cells), and intercellular communication (fibroblasts as stronger signal senders to malignant tumor cells). These findings confirm that PSCs cannot accurately represent fibroblasts in PDAC. We emphasize that clarifying these points will not undermine the study’s significance but will strengthen its rigor and comparability. Wang et al.’s work remains a valuable contribution to understanding PDAC progression, and we anticipate these clarifications will further advance stromal-immune crosstalk research in PDAC.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":" ","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13196156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis as a therapeutic target in cancer: mechanisms, immune interactions, and emerging strategies.","authors":"Bufu Tang,Yaling Lin,Songhua Cai,Jingqin Ma,Wei Zhang,Tong Jiang,Ruiqing Gao,Yongjie Zhou,Xuran Jin,Yuyu Guan,Wen Zhang,Lingxiao Liu,Zhiping Yan,Peng Luo,Xudong Qu","doi":"10.1186/s12943-026-02590-0","DOIUrl":"https://doi.org/10.1186/s12943-026-02590-0","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"18 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM29 promotes pancreatic cancer MVI via IκBα K48-ubiquitination and NF-κB activation in CXCL5⁺ epithelial cells.","authors":"Long Liu,Zhenzhen Gao,Qi Wang,Xiaohong Zhao,Fabiao Zhang,Yu Zhu,Wangyang Sun,Yuxi Huang,Zhenbo Wang,Sheng Yan,Shaowei Li,Yu Zhang","doi":"10.1186/s12943-026-02652-3","DOIUrl":"https://doi.org/10.1186/s12943-026-02652-3","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"56 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147636014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Composite proteomic and metabolomic plasma biomarkers for detection of colorectal, lung and ovarian cancers.","authors":"Jim Åkerrén Ögren, Joakim Ekström, Natallia Rameika, Emma Torell, Chatarina Larsson, Ivaylo Stoimenov, Patrick Micke, Ulf Gyllensten, Mats Hellström, Bengt Glimelius, Karin Stålberg, Tobias Sjöblom","doi":"10.1186/s12943-026-02654-1","DOIUrl":"10.1186/s12943-026-02654-1","url":null,"abstract":"<p><p>BACKGROUND: Sensitive and specific blood biomarkers for early detection of colorectal (CRC), lung (LuCa) and ovarian (OvCa) cancers are highly warranted. The current blood tests often need to be complemented with other clinical methods to achieve adequate diagnostic performance. Recent progress in the molecular profiling of plasma from cancer patients holds potential for improved non-invasive screening. Here, we aimed to identify composite proteomic and metabolomic plasma biomarkers for early cancer detection with performances that exceed those of existing FDA-approved blood and stool-based diagnostic tests for CRC, LuCa and OvCa. METHODS: In a case-control study using samples from the U-CAN and EpiHealth biobanks, we measured plasma levels of 165 proteins and 244 metabolites in 818 patients with CRC, LuCa and OvCa at diagnosis, 119 patients with non-malignant conditions of the corresponding organs, and 1,129 healthy individuals. We performed an exhaustive search over all cut-off values of the ROC for all combinations of up to 4 proteins and metabolites, implementing measures to minimize the impact of cross-cohort comparisons. Ultimately, we benchmarked candidate biomarkers performance to FDA approved blood tests in clinical use for detection of cancer. External validation was performed using publicly available datasets. RESULTS: We found biomarkers composed of 2–4 proteins separating cases of each tumor type from healthy controls with ROC AUC, respectively for CRC: CEACAM5, FLT1, IL19, Ferritin (AUC 0.89), LuCa: FNDC5, MDK, PLAUR, CEACAM5 (AUC 0.91) and OvCa: MUC16/CA125, PLG (AUC 0.97). The diagnostic performance of these biomarkers was comparable to, and in some instances surpassed, the performance of established tests, such as Epi proColon (AUC 0.82) and Cologuard (AUC 0.93). Metabolites were informative for tumor stage discrimination, especially in LuCa and OvCa. External validation in the CancerSeek dataset showed strong agreement in biomarker performance. CONCLUSIONS: The composite protein biomarkers identified in this study represent a novel opportunity for detection, staging and differential diagnosis of common tumor types. Metabolites are more relevant for tumor staging than early detection. A limited number of well-performing analytes enables cost-effective implementation in clinical diagnostics and merits further evaluation. </p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":" ","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13081656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ROCK1 inhibition primes anti-tumor immunity in EGFR-mutant NSCLC by triggering PD-L1 degradation mediated by SMURF2.","authors":"Menglin Bai, Qianqian Gao, Peng Jin, Lin Ma, Ji Li, Leilei Wu, Weiqing Wang, Luojia Lv, Yintao Li, Bo Cheng, Jinming Yu, Xue Meng","doi":"10.1186/s12943-026-02653-2","DOIUrl":"10.1186/s12943-026-02653-2","url":null,"abstract":"<p><p>Epidermal growth factor receptor (EGFR) mutations are common in non-small-cell lung cancer (NSCLC) but typically confer poor responses to immunotherapy, likely owing to an inhibitory tumor immune microenvironment. Here, Rho-associated coiled-coil containing protein kinase 1 (ROCK1) was identified as having significantly elevated kinase activity in EGFR-mutant NSCLC through phosphoproteomic analyses. Inhibition of ROCK1, while only mildly suppressing tumor cell proliferation, markedly enhances CD8 + T cell-mediated antitumor immune responses in vitro and in vivo. Mechanistically, ROCK1 inhibition suppresses PD-L1 expression via GSK3α-mediated phosphorylation of PD-L1 at serine 283, promoting its ubiquitination and degradation by the E3 ubiquitin ligase SMURF2. This process enhances the cytotoxic activity of CD8 + T cells. Furthermore, combining ROCK1 inhibitors with PD-L1 blockade produces substantial anti-tumor efficacy in EGFR-mutant NSCLC mouse models. Collectively, our findings reveal a critical role for ROCK1 in regulating the tumor immune microenvironment and highlight that targeting ROCK1 could improve immunotherapy outcomes in patients with EGFR-mutant NSCLC.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":" ","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging evidence on micro- and nanoplastics carcinogenicity: mechanisms, models, and signaling networks.","authors":"Mohamed Alaraby, Doaa Abass, Ricard Marcos, Alba Hernández","doi":"10.1186/s12943-026-02657-y","DOIUrl":"10.1186/s12943-026-02657-y","url":null,"abstract":"<p><p>Evidence of micro- and nanoplastics (MNPLs) presence in human tissues, cells, and biological fluids raises concerns about their potential role in hazardous diseases, including cancer. Higher concentrations of microplastics (MPLs) in cancerous tissues compared with adjacent healthy tissues, particularly in barrier organs such as the lungs, intestines, and reproductive system, suggest a potential association with tissue pathology and tumor-related processes. Extracted MNPLs from cancerous tissues exhibit diverse polymer compositions and morphologies, predominantly fibers and fragments larger than 1 μm, while smaller nanoplastics (NPLs) are likely underrepresented due to detection limitations. To investigate how MNPLs promote carcinogenesis depending on their physicochemical characteristics, various in vitro and in vivo studies have been analyzed. Most studies use pristine commercial spherical polystyrene (PS) MNPLs, which do not fully exhibit real-life MNPL characteristics but still provide valuable insights into their hazardous effects across a wide size range. Additional studies employing alternative polymers and environmentally relevant particle shapes further advance understanding of MNPL-associated health risks, as addressed in this review. Existing data indicates that smaller NPLs readily cross biological barriers and accumulate within cells due to their high surface area, whereas larger MPLs primarily interact at tissue surfaces, causing physical stress, tight junction disruption, and microbiota perturbation. Notably, MNPL exposure induces multiple hazardous effects and disrupts cellular homeostasis through coordinated and integrated signaling pathways. NF-κB signaling triggers pro-inflammatory and survival gene expression, while JNK-MAPK, ERK1/2-MAPK, and JAK–STAT pathways amplify inflammation, DNA damage responses, and apoptosis. MNPLs also induce ROS-driven ER stress, mitochondrial dysfunction, and dysregulation of AKT, TP53, caspases, and XIAP, activating apoptosis, necroptosis, and fibrosis. Compensatory antioxidant responses are activated via NRF2/HO-1 to counteract oxidative stress, while β-catenin/Wnt signaling is concurrently modulated, linking ROS-induced stress to tumorigenic reprogramming and cellular proliferation. Dysregulation of metabolic and growth regulators, including PI3K–AKT–mTOR, AMPK, mTORC1, and P70S6K, promotes cellular proliferation, survival, and metabolic adaptation. Simultaneously, modulation of ECM–receptor interactions, focal adhesion, Hippo, TGF-β, and cell-cycle regulators (CDK4/6, Cyclin D1, p-Rb) reshapes the tumor microenvironment, supporting potential malignant progression. All these interconnected events establish a tumor-permissive environment, promoting uncontrolled proliferation, metabolic reprogramming, and malignant transformation, thereby supporting the potential role of MNPLs in carcinogenesis.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":" ","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-coding RNAs: modulators of signaling pathways and prognostic biomarkers in digestive system cancer.","authors":"Guoming Chen,Yinglan Liang,Ying Yan,Jiayi Zou,Jiayi Zhang,Xiaotong Zeng,Liangman Xiao,Cheng Zhang,Yibin Feng","doi":"10.1186/s12943-025-02549-7","DOIUrl":"https://doi.org/10.1186/s12943-025-02549-7","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"3 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147583932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}