Molecular Cancer最新文献

Modulation of tumor-derived exosomes and reprogramming of cancer-associated fibroblasts for colorectal cancer therapy. 肿瘤源性外泌体的调节和结直肠癌治疗中癌症相关成纤维细胞的重编程。

IF 33.9 1区医学

Molecular Cancer Pub Date : 2026-05-06 DOI: 10.1186/s12943-026-02661-2

Susu Han, Tao Huang, Xiaoling Yin, Ting Wang, Qi Shi, Yufei Tang, Tingting Zhu, Song Gao, Hua Sui, Fenggang Hou

{"title":"Modulation of tumor-derived exosomes and reprogramming of cancer-associated fibroblasts for colorectal cancer therapy.","authors":"Susu Han, Tao Huang, Xiaoling Yin, Ting Wang, Qi Shi, Yufei Tang, Tingting Zhu, Song Gao, Hua Sui, Fenggang Hou","doi":"10.1186/s12943-026-02661-2","DOIUrl":"https://doi.org/10.1186/s12943-026-02661-2","url":null,"abstract":"Hypoxia is pervasive within the solid tumor microenvironment (TME), reshaping it through exosome release. As the main component of the tumor stroma, fibroblasts influence TME remodeling and tumor progression. Recent advances in targeting tumor-derived exosomes offer promising opportunities for innovative colorectal cancer (CRC) therapies. Here, we found that exosomes induced by hypoxia in CRC cells (H-Exo) can promote the activation of normal tissue-associated fibroblasts (NAFs) into cancer-associated fibroblasts (CAFs) phenotype, with a stronger effect compared to normoxic exosomes (N-Exo). Machine learning analysis identified HIF1A-AS2, induced by hypoxic tumor-derived exosomes, as a promising prognostic lncRNA in CRC. Pan-cancer and scRNA-seq analyses showed that high HIF1A-AS2 expression was characterized by hypoxia, angiogenesis, immunosuppression (e.g., CAFs), TGF-β, and fibroblast-CD44 interactions in CRC. HIF1A-AS2 expression progressively increased along pseudotime, shifting from early immune activation to late-stage extracellular matrix (ECM) organization, vascular niche formation, and fibroblast activation. HIF1A-AS2 in H-Exo was a key factor in the transformation of NAFs into CAFs. Exosomal HIF1A-AS2 sequesters miR-33, thereby derepressing HIF-1α, activating Notch1/ERK signaling, and upregulating angiogenic and matrix-remodeling factors (e.g., VEGF, MMP-7, and MMP-9). Further research revealed that exosomes with silenced HIF1A-AS2 or overexpressed miR-33 could inhibit CAF infiltration, tumor cell proliferation, angiogenesis, and ECM reorganization in xenografts, ultimately suppressing tumor growth. These findings highlight that simultaneously blocking tumor exosome-driven fibroblast activation and the HIF1A-AS2/miR-33/HIF-1α axis may serve as a promising therapeutic avenue for CRC intervention.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":" ","pages":""},"PeriodicalIF":33.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840495","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}

引用次数: 0

Non-coding RNAs as master regulators of ferroptosis in cancer: mechanisms and clinical implications. 非编码rna作为癌症铁下垂的主要调节因子：机制和临床意义。

IF 33.9 1区医学

Molecular Cancer Pub Date : 2026-05-06 DOI: 10.1186/s12943-026-02666-x

Haoyang Mo, Yao Xie, Hao Zhang, Yunyi Liu, Wantao Wu, Zhiwei Xia, Peng Luo, Zhixiong Liu, Quan Cheng

{"title":"Non-coding RNAs as master regulators of ferroptosis in cancer: mechanisms and clinical implications.","authors":"Haoyang Mo, Yao Xie, Hao Zhang, Yunyi Liu, Wantao Wu, Zhiwei Xia, Peng Luo, Zhixiong Liu, Quan Cheng","doi":"10.1186/s12943-026-02666-x","DOIUrl":"https://doi.org/10.1186/s12943-026-02666-x","url":null,"abstract":"Ferroptosis is a non-apoptotic form of cell death characterized by intracellular iron accumulation and the subsequent elevation of cytotoxic lipid peroxides. Various cellular metabolic pathways intricately regulate this process, including redox homeostasis, iron metabolism, lipid metabolism, and other signaling cascades. Increasing evidence substantiates the critical role of ferroptosis in tumorigenesis and cancer therapy. However, our current understanding of numerous mechanisms underlying tumor ferroptosis remains limited. Noncoding RNAs (ncRNAs) provide a new perspective. Several ncRNAs, particularly microRNAs, long noncoding RNAs, and circular RNAs, are being demonstrated to form a comprehensive regulatory network that exerts direct regulation over ferroptosis-related genes or enzymes while indirectly modulating regulatory factors associated with ferroptosis. Strikingly, ncRNAs also serve as crucial mediators orchestrating communication between cancer cells, stromal cells, and immune cells within the tumor microenvironment (TME). Given their substantial potential in tumors and the TME, ferroptosis-related RNAs emerge as promising targets for immunotherapy and overcoming drug resistance. The development of novel nanomedicines for delivering ncRNAs is crucial in advancing antitumor therapy. This review comprehensively elucidates the regulatory mechanisms of ferroptosis-associated ncRNAs across various cancers, sheds light on their functions within the TME, explores their clinical potential to overcome drug resistance, and highlights unresolved questions.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":" ","pages":""},"PeriodicalIF":33.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840528","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}

引用次数: 0

Testosterone and cancers: biological functions, molecular mechanisms and therapy. 睾酮与癌症：生物学功能、分子机制和治疗。

IF 33.9 1区医学

Molecular Cancer Pub Date : 2026-05-06 DOI: 10.1186/s12943-026-02676-9

Zhixiang Zhou, Tengda Huang, Jiaxin Li, Li Fu, Lin Xu, Xuping Feng, Zheng Zhang, Hongyuan Pan, Ke Qin, Xinyi Zhou, Yan Xiang, Kefei Yuan

{"title":"Testosterone and cancers: biological functions, molecular mechanisms and therapy.","authors":"Zhixiang Zhou, Tengda Huang, Jiaxin Li, Li Fu, Lin Xu, Xuping Feng, Zheng Zhang, Hongyuan Pan, Ke Qin, Xinyi Zhou, Yan Xiang, Kefei Yuan","doi":"10.1186/s12943-026-02676-9","DOIUrl":"https://doi.org/10.1186/s12943-026-02676-9","url":null,"abstract":"Testosterone, the principal androgen in humans, plays an essential role in maintaining physiological homeostasis. In recent years, accumulating evidence has implicated testosterone in the progression of diverse malignancies, underscoring its context-dependent roles in tumor biology. A series of studies suggest that testosterone can act through canonical androgen receptor (AR) signaling as well as non-canonical, AR-related mechanisms to modulate membrane receptor-mediated signal transduction, metabolic reprogramming, and the tumor immune microenvironment, thereby fostering tumor growth, metastasis, maintenance of stemness, and the development of therapy resistance. Notably, interventional strategies targeting testosterone/androgen signaling have entered clinical investigation and have demonstrated therapeutic promise. Beyond the best-developed clinical paradigms of prostate and breast cancer, we also highlight hepatocellular carcinoma and cutaneous melanoma as informative additional contexts that broaden the understanding of testosterone biology across cancers. Here, we propose that testosterone is best understood not simply as a hormonal input into isolated cancer pathways, but as a systems-level endocrine regulator of tumor plasticity that integrates transcriptional programs, rapid kinase signaling, and membrane receptor-associated responses across distinct tumor contexts. Within this framework, membrane androgen signaling is considered an emerging but still largely preclinical therapeutic vulnerability, whereas androgen-directed interventions in prostate and breast cancer represent the most clinically mature translational paradigms.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":" ","pages":""},"PeriodicalIF":33.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840490","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}

引用次数: 0

Correction: Targeting mitochondrial homeostasis as a cancer treatment strategy: current status and future prospects. 校正：靶向线粒体稳态作为癌症治疗策略：现状和未来前景。

IF 33.9 1区医学

Molecular Cancer Pub Date : 2026-05-02 DOI: 10.1186/s12943-026-02664-z

Honglin Zhong, Renjie Pan, Yuzhen Ouyang, Tengfei Xiao, Wangning Gu, Hongmin Yang, Hui Wang, Hucheng Li, Tianfang Peng, Pan Chen

引用次数: 0

Correction: Circular RNA F-circSR derived from SLC34A2-ROS1 fusion gene promotes cell migration in non-small cell lung cancer. 更正：源自SLC34A2-ROS1融合基因的环状RNA F-circSR促进非小细胞肺癌的细胞迁移。

IF 33.9 1区医学

Molecular Cancer Pub Date : 2026-05-02 DOI: 10.1186/s12943-026-02672-z

Ke Wu, Xun Liao, Youling Gong, Juan He, Jian-Kang Zhou, Shuangyan Tan, Wenchen Pu, Canhua Huang, Yu-Quan Wei, Yong Peng

引用次数: 0

A non-complement role for C1R rewires integrin and death-receptor signaling to drive renal cancer metastasis. C1R的非补体作用重新连接整合素和死亡受体信号以驱动肾癌转移。

IF 33.9 1区医学

Molecular Cancer Pub Date : 2026-05-01 DOI: 10.1186/s12943-026-02677-8

Haotian Wei, Shenglong Li, Shimiao Zhu, Chenglong Xu, Yue Wang, Zhaochen Li, Yujing Guan, Jiahang Li, Runze Jiang, Xianglian Ge, Tailong Yi, Xing Xu, Yang Xie, Jing Tian, Yingzhe Piao, Ping Zhang, Changyi Quan, Xun Jin

{"title":"A non-complement role for C1R rewires integrin and death-receptor signaling to drive renal cancer metastasis.","authors":"Haotian Wei, Shenglong Li, Shimiao Zhu, Chenglong Xu, Yue Wang, Zhaochen Li, Yujing Guan, Jiahang Li, Runze Jiang, Xianglian Ge, Tailong Yi, Xing Xu, Yang Xie, Jing Tian, Yingzhe Piao, Ping Zhang, Changyi Quan, Xun Jin","doi":"10.1186/s12943-026-02677-8","DOIUrl":"https://doi.org/10.1186/s12943-026-02677-8","url":null,"abstract":"Background: Metastasis is the leading cause of death in clear cell renal cell carcinoma (ccRCC) patients. Anoikis, a form of programmed cell death induced by the loss of cell-extracellular matrix interactions, is a critical factor in hindering metastasis. Nevertheless, the regulatory mechanisms underlying anoikis resistance in ccRCC remain poorly characterized and warrant further investigation.Methods: We created a single-cell transcriptomic atlas of ccRCC metastasis and used multi-omics data to identify the key role of complement C1R during metastasis. Anoikis-related cell experiments and mouse models were conducted to assess the impact of C1R on anoikis resistance and metastatic potential. Transcriptome sequencing, immunoprecipitation, molecular docking, truncation construction, and immunofluorescence were used to explore how C1R induces anoikis resistance. The mouse lung metastasis model was employed to validate the efficacy of a novel combination drug regimen.Results: Our study identifies complement C1R as a crucial regulator of ccRCC metastasis by enhancing anoikis resistance. ITGB1 and FAF1 have been recognized as crucial downstream targets of C1R. Specifically, C1R promotes anoikis resistance by facilitating ITGB1 endocytosis to activate the Akt/Erk pathway and by inhibiting FAF1-FAS binding to block the Fas/FasL pathway. Moreover, our findings indicate that the combined use of the ITGB1 inhibitor (ATN161) and the Fas/FasL pathway activator (Edelfosine) significantly suppresses ccRCC metastasis.Conclusion: C1R functions as a pivotal driver of ccRCC metastasis through dual mechanisms, and therapeutic strategies targeting C1R may offer a promising approach to inhibit metastasis.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":" ","pages":""},"PeriodicalIF":33.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817880","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}

引用次数: 0

Adjuvant recombinant human endostatin combined with toripalimab (anti-PD-1) in locally advanced melanoma: an exploratory phase 2 clinical trial incorporating single-cell RNA/TCR/BCR sequencing. 佐剂重组人内皮抑素联合多利帕利单抗（抗pd -1）治疗局部晚期黑色素瘤：一项采用单细胞RNA/TCR/BCR测序的探索性2期临床试验

IF 37.3 1区医学

Molecular Cancer Pub Date : 2026-04-27 DOI: 10.1186/s12943-026-02675-w

Xianglin Hu,Yu Xu,Zixin Wang,Lingge Yang,Biqiang Zheng,Feifan Sun,Dongsong Liu,Bochong Shi,Haoyu Zheng,Xin Liu,Lin Yu,Shengjian Zhang,Yan Yan,Wangjun Yan,Yangbai Sun,Yong Chen,Chunmeng Wang

引用次数: 0

Endoplasmic reticulum stress in antitumor immunity and immunotherapy resistance: mechanisms and therapeutic implications. 内质网应激在抗肿瘤免疫和免疫治疗抵抗中的作用：机制和治疗意义。

IF 37.3 1区医学

Molecular Cancer Pub Date : 2026-04-27 DOI: 10.1186/s12943-026-02674-x

Yingfan Zhao,Yunzhi Shang,Ting Luan,Zhong Yu,Yang Yue,Xing Niu,Hui Li,Shizhuo Wang,Ce Wang,Lu Liu

引用次数: 0

Metabolic reprogramming and molecular crosstalk at the cancer-endothelial interface in ovarian carcinoma. 卵巢癌细胞内皮界面的代谢重编程和分子串扰。

IF 37.3 1区医学

Molecular Cancer Pub Date : 2026-04-27 DOI: 10.1186/s12943-026-02673-y

Bruna Sousa,Adele Chiavassa,Leonor Delgado,Rafael Gomes,Cindy Mendes,Jacinta Serpa

引用次数: 0

Breast cancer immunotherapy: mechanisms of immune evasion, biomarkers, and emerging therapeutic strategies. 乳腺癌免疫治疗：免疫逃避机制、生物标志物和新兴治疗策略。