Molecular Cancer最新文献

{"title":"Evolution of direct RAS inhibitors: from undruggable target to clinical breakthroughs","authors":"Xia Wang, Jing Wu, Aotian Xiao, Jie Wang, Jun Tian","doi":"10.1186/s12943-025-02364-0","DOIUrl":"https://doi.org/10.1186/s12943-025-02364-0","url":null,"abstract":"The RAS signaling pathway, particularly through mutations in KRAS, NRAS, and HRAS, plays a pivotal role in driving oncogenesis in a wide range of cancers. For years, RAS proteins were deemed \"undruggable\" due to their smooth surface and lack of deep binding pockets. However, recent breakthroughs in targeting specific RAS mutations, particularly KRASG12C, have revolutionized the field. The discovery of covalent inhibitors that bind to an allosteric pocket near the cysteine residue of KRASG12C has led to the development of FDA-approved drugs, marking a significant milestone in RAS-targeted therapy. This review provides a comprehensive overview of the evolution of direct RAS inhibitors, focusing on the chemical development of small molecule inhibitors, molecular glues, protein degraders, and other emerging strategies. We highlight the structural evolution of KRAS inhibitors, from covalent fragment-based approaches to non-covalent inhibitors and pan-RAS targeting strategies. Additionally, we discuss the clinical progress of key inhibitors, including their efficacy, resistance mechanisms, and combination treatment options. Finally, this review explores other innovative approaches such as cyclopeptide inhibitors and outlines future directions of RAS-targeting strategies. The success of RAS-targeted therapies underscores the transformative potential of overcoming the \"undruggable\" nature of RAS, offering new hope for patients with RAS-driven cancers.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"2 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133541","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":"Retraction Note: Long non-coding RNA PVT1 promotes tumor progression by regulating the miR-143/HK2 axis in gallbladder cancer","authors":"Jianan Chen, Yan Yu, Hua Li, Qiuyue Hu, Xiaolong Chen, Yuting He, Chen Xue, Fang Ren, Zhigang Ren, Juan Li, Liwen Liu, Zhenfeng Duan, Guangying Cui, Ranran Sun","doi":"10.1186/s12943-025-02452-1","DOIUrl":"https://doi.org/10.1186/s12943-025-02452-1","url":null,"abstract":"This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12943-019-0947-9.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"27 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995497","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":"Correction: Bridging the tumor microenvironment: the pivotal role of cancer-associated fibroblasts in tumor cachexia development","authors":"Guoming Chen, Bonan Chen, Yilin Wu, Hao Nie, Zilan Zhong, Shuyang Yang, Rui Qin, Wei Kang, Cheng Zhang, Ning Wang, Yibin Feng","doi":"10.1186/s12943-025-02453-0","DOIUrl":"https://doi.org/10.1186/s12943-025-02453-0","url":null,"abstract":"<p><b>Correction: Mol Cancer 24</b>,<b> 194 (2025)</b></p><p><b> https://doi.org/10.1186/s12943-025-02379-7</b></p><p>Following publication of the original article [1], the author reported that the Figure 2 is repeatedly captured as Figure 4. The incorrect and correct Figure 4 are provided below. The original article has been corrected.</p><p>Incorrect Figure 4:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02453-0/MediaObjects/12943_2025_2453_Figa_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure a\" aria-describedby=\"Figa\" height=\"825\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02453-0/MediaObjects/12943_2025_2453_Figa_HTML.png\" width=\"685\"/></picture></figure><p>Correct Figure 4:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02453-0/MediaObjects/12943_2025_2453_Figb_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure b\" aria-describedby=\"Figb\" height=\"592\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02453-0/MediaObjects/12943_2025_2453_Figb_HTML.png\" width=\"685\"/></picture></figure><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Chen G, Chen B, Wu Y, et al. Bridging the tumor microenvironment: the pivotal role of cancer-associated fibroblasts in tumor cachexia development. Mol Cancer. 2025;24:194. https://doi.org/10.1186/s12943-025-02379-7.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><span>Author notes</span><ol><li><p>Guoming Chen and Bonan Chen contributed equally to this work.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China</p><p>Guoming Chen, Cheng Zhang, Ning Wang & Yibin Feng</p></li><li><p>Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China</p><p>Bonan Chen & Wei Kang</p></li><li><p>The Shenzhen Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Shenzhen, China</p><p>Yilin Wu & Zilan Zhong</p></li><li><p>The Foshan Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, China</p><p>Hao Nie</p></li><li><p>The Second Clinical Medical College of Guangzhou, University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China</p><p>Shuyang Yang</p></li><li><p>The First Clinic","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"21 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987568","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":"Engineered iron oxide nanoplatforms: reprogramming immunosuppressive niches for precision cancer theranostics","authors":"Chao Yang, Shenglong Li, Liming Wang","doi":"10.1186/s12943-025-02443-2","DOIUrl":"https://doi.org/10.1186/s12943-025-02443-2","url":null,"abstract":"Iron oxide nanoparticles (IONPs) have transitioned from conventional magnetic resonance imaging (MRI) contrast agents into structurally programmable combined imaging/treatment tools, leveraging their superparamagnetism, catalytic activity, and surface engineering versatility to achieve spatiotemporal control over drug delivery and immune modulation. Advances in nanofabrication now yield size-optimized aggregates with enhanced tumor accumulation through the enhanced permeability and retention (EPR) effect, while clinically approved formulations like ferumoxytol demonstrate intrinsic immunomodulatory functionality, positioning IONPs as pivotal tools for precision oncology. Conversely, cancer immunotherapy remains limited by the immunosuppressive tumor microenvironment (TME), where cellular suppression via M2-polarized macrophages and regulatory T cells (Tregs) synergizes with physical exclusion from dense extracellular matrices and metabolic sabotage through lactate-driven acidosis. These barriers establish “immune-cold” phenotypes characterized by deficient CD8⁺ T-cell infiltration and tertiary lymphoid structure formation, driving checkpoint inhibitor resistance with sub-30% response rates in solid tumors. To overcome these constraints, IONPs orchestrate multimodal immunotherapeutic strategies: they reprogram suppressive niches by polarizing macrophages toward M1 phenotypes, activate STING pathways, and induce immunogenic ferroptosis; enable precision delivery via magnetic lymph node targeting and cancer cell membrane-mediated homologous tumor homing; and facilitate real-time theranostics through MRI/magnetic particle imaging (MPI)-monitored immune cell trafficking. Preclinical validation confirms synergistic efficacy, with combinatorial regimens achieving over 50% complete tumor regression by converting immunologically cold microenvironments into inflamed states. This review systematically explores cutting-edge IONP-based innovations—spanning immune cell engineering, biohybrid systems, and energy-amplified therapies—that bridge localized tumor eradication with systemic antitumor immunity, while critically evaluating translational barriers for clinical implementation. ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"15 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144924065","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":"Advances in novel cell death mechanisms in breast cancer: intersecting perspectives on ferroptosis, cuproptosis, disulfidptosis, and pyroptosis","authors":"Zhengjun Jing, Wenqin Huang, Jun Mei, Sudhanshu Bhushan, Xinhong Wu, Chengbiao Yan, Hongmei Zheng, Yalong Yang","doi":"10.1186/s12943-025-02445-0","DOIUrl":"https://doi.org/10.1186/s12943-025-02445-0","url":null,"abstract":"The advent of molecular classification has ushered breast cancer treatment into the era of precision medicine. Nevertheless, clinical management continues to face significant challenges posed by drug resistance and tumor heterogeneity. Recent advances have identified novel programmed cell death (PCD) mechanisms-including ferroptosis, cuproptosis, disulfidptosis, and pyroptosis-as critical regulators of breast cancer progression, therapeutic responsiveness, and immune microenvironment remodeling. This review systematically elucidates the mechanistic foundations of these PCD pathways and investigates their molecular regulatory networks within breast cancer pathogenesis. Furthermore, we evaluate current targeted intervention strategies and assess their clinical translation potential, ultimately providing a theoretical framework for pioneering therapeutic approaches.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"23 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905984","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":"Retraction Note: m6A demethylase ALKBH5 inhibits pancreatic cancer tumorigenesis by decreasing WIF-1 RNA methylation and mediating Wnt signaling","authors":"Min Kang, Yunshan Wang, Yan Wang, Yin Bi, Songqing He, Fumio Shimamoto, Bo Tang, Yihua Yang","doi":"10.1186/s12943-025-02432-5","DOIUrl":"https://doi.org/10.1186/s12943-025-02432-5","url":null,"abstract":"This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12943-019-1128-6.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"36 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899257","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":"Single-cell multi-omics in cancer immunotherapy: from tumor heterogeneity to personalized precision treatment","authors":"Jiayuan Le, Yating Dian, Deze Zhao, Ziyu Guo, Zehao Luo, Xiang Chen, Furong Zeng, Guangtong Deng","doi":"10.1186/s12943-025-02426-3","DOIUrl":"https://doi.org/10.1186/s12943-025-02426-3","url":null,"abstract":"Cancer immunotherapy has revolutionized clinical oncology; however, the inherent complexity and heterogeneity of cancer present substantial challenges to achieving broad therapeutic efficacy. Tumor heterogeneity manifests not only among different patients but also within individual tumors, further complicating personalized treatment approaches. Single-cell sequencing technologies encompassing genomics, transcriptomics, epigenomics, proteomics, and spatial omics have significantly enhanced our ability to dissect tumor heterogeneity at single-cell resolution with multi-layered depth. These approaches have illuminated tumor biology, immune escape mechanisms, treatment resistance, and patient-specific immune response mechanisms, thereby substantially advancing precision oncology strategies. This review systematically examines recent advances in single-cell multi-omics technologies across various cancer research areas, emphasizing their transformative impacts on understanding tumor heterogeneity, immunotherapy, minimal residual disease monitoring, and neoantigen discovery. Additionally, we discuss current technical and analytical limitations and unresolved questions associated with single-cell technologies. We anticipate single-cell multi-omics technologies will become central to precision oncology, facilitating truly personalized therapeutic interventions.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"26 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899213","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":"The application of organoids in treatment decision-making for digestive system cancers: progress and challenges","authors":"Yufei Wang, Limin Zhang, Louis Zizhao Wang, Yang Cao, Lulu Huang, Gautam Sethi, Xiaoguang Chen, Lingzhi Wang, Boon-Cher Goh","doi":"10.1186/s12943-025-02429-0","DOIUrl":"https://doi.org/10.1186/s12943-025-02429-0","url":null,"abstract":"Digestive system cancers—including gastric, liver, colorectal, esophageal, and pancreatic malignancies—remain leading causes of cancer death, with treatment resistance posing major challenges in advanced disease. Patient-derived cancer organoids (PDCOs), 3D mini-tumors grown from patient biopsies, have revolutionized personalized oncology by faithfully replicating tumor biology and enabling predictive drug testing for chemotherapy, radiotherapy, targeted therapy, and immunotherapy. While demonstrating good predictive accuracy, current limitations include incomplete tumor microenvironments, variable establishment rates, and lengthy processing times. Emerging technologies like AI, organ-on-chip systems, and 3D bioprinting are addressing these challenges, while clinical trials explore applications in neoadjuvant therapy and real-time treatment guidance. This Review highlights key advances in PDCO technology and its transformative potential for treatment decision-making in digestive system cancers, bridging laboratory research with clinical care to enable truly personalized therapeutic strategies tailored to individual tumor biology.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"47 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899110","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":"Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities","authors":"Lan Hu, Zikun Huang, Zhaoyong Liu, Ying Zhang","doi":"10.1186/s12943-025-02428-1","DOIUrl":"https://doi.org/10.1186/s12943-025-02428-1","url":null,"abstract":"Biomolecular phase separation has emerged as a fundamental mechanism governing intracellular spatial organization and functional compartmentalization, and is increasingly recognized as a critical factor in tumor initiation and progression. Through multivalent molecular interactions, biomolecular phase separation contributes to the formation of condensates that mediate the assembly of membraneless organelles, coordination of signaling pathways, and transcriptional programs. Under physiological conditions, condensation contributes to the maintenance of gene expression homeostasis, stress adaptation, and metabolic balance. In cancer cells, however, biomolecular condensates (BMCs) often exhibit aberrant behavior, accompanied by alterations in their structure, components, and regulatory mechanisms. Such perturbations may disrupt cellular homeostasis and influence key biological processes including gene regulation, signal transduction, metabolic reprogramming, and immune responses, thereby modulating various cancer hallmarks. Although the mechanistic understanding of BMCs remains incomplete, their intrinsic plasticity and environmental sensitivity make them attractive therapeutic targets for cancer treatment. This review provides a comprehensive overview of the regulatory factors and functional mechanisms of BMCs in cancer biology, with a particular focus on their involvement in diverse cancer hallmarks. This review further summarizes emerging therapeutic strategies targeting condensation, aiming to inspire novel treatment opportunities.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"12 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899143","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":"Oxidative stress in cancer: from tumor and microenvironment remodeling to therapeutic frontiers","authors":"Xisong Liang, Jiadi Weng, Zhongyi You, Yang Wang, Jie Wen, Zhiwei Xia, Shaorong Huang, Peng Luo, Quan Cheng","doi":"10.1186/s12943-025-02375-x","DOIUrl":"https://doi.org/10.1186/s12943-025-02375-x","url":null,"abstract":"Oxidative stress is a pathological condition of redox signaling dysregulation and macromolecular oxidative damage arising from elevated ROS levels. Oxidative stress interacts with tumor cell growth regulation and tumor microenvironment remodeling, and has been a critical hallmark of cancer. Targeting oxidative stress has garnered great attention in cancer therapy development. However, it is still challenging due to the complexity and heterogeneity of oxidative stress regulation across different cancers, and this encourages a comprehensive understanding of the oxidative stress network in cancers to overcome this obstacle. Therefore, we introduced the oxidative stress generation and regulatory network within tumor cells and discussed their roles in both tumor cells and the tumor microenvironment. Subsequently, we summarized the current therapeutic strategies and highlighted emerging clinical applications, providing an up-to-date overview of oxidative stress-based approaches. Particularly, their cross-application with immunotherapy and nanomedicine has provided an excellent opportunity to integrate multiple effects, exhibiting surpassing advantages. This review elaborates on oxidative stress in cancer biology and its therapeutic implications. By integrating current knowledge and the emerging coordination with immunotherapy and nanomedicine, we underscore the potential of oxidative stress-targeting approaches. Future research on overcoming therapeutic resistance and developing compatible platforms to combine multiple approaches will pave the way to cancer elimination.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"9 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899144","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}