Molecular Cancer最新文献

{"title":"Correction: METTL3 facilitates tumor progression via an m6A-IGF2BP2-dependent mechanism in colorectal carcinoma","authors":"Ting Li,Pei-Shan Hu,Zhixiang Zuo,Jin-Fei Lin,Xingyang Li,Qi-Nian Wu,Zhan-Hong Chen,Zhao-Lei Zeng,Feng Wang,Jian Zheng,Demeng Chen,Bo Li,Tie-Bang Kang,Dan Xie,Dongxin Lin,Huai-Qiang Ju,Rui-Hua Xu","doi":"10.1186/s12943-026-02780-w","DOIUrl":"https://doi.org/10.1186/s12943-026-02780-w","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"27 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893796","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: Multimodal sequencing identifies synergistic mechanisms driving resistance to neoadjuvant nivolumab treatment in hepatocellular carcinoma.","authors":"Fanhong Zeng, Jiaxin Guo, Zheng Zeng, Vanilla Xin Zhang, Yu-Man Tsui, Po-Man Li, Abdullah Husain, Qingyang Zhang, Joyce Man-Fong Lee, Tan-To Cheung, Daniel Wai-Hung Ho, Irene Oi-Lin Ng","doi":"10.1186/s12943-026-02777-5","DOIUrl":"10.1186/s12943-026-02777-5","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886937","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: Human epididymis protein 4 in association with Annexin II promotes invasion and metastasis of ovarian cancer cells.","authors":"Huiyu Zhuang, Mingzi Tan, Juanjuan Liu, Zhenhua Hu, Dawo Liu, Jian Gao, Liancheng Zhu, Bei Lin","doi":"10.1186/s12943-026-02779-3","DOIUrl":"10.1186/s12943-026-02779-3","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851048","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":"Deep molecular profiling of lung neuroendocrine tumours and supra-carcinoids.","authors":"Alexandra Sexton-Oates, Émilie Mathian, Noah Candeli, Yuliya Lim, Catherine Voegele, Alex Di Genova, Laurane Mangé, Zhaozhi Li, Tijmen van Weert, Lipika Kalson, Tiffany M Delhomme, Lisa M Hillen, Ricardo Blázquez-Encinas, Abel Gonzalez-Perez, Maike L Morrison, Eleonora Lauricella, Lise Mangiante, Lisa Bonheme, Laura Moonen, Gudrun Absenger, Janine Altmuller, Cyril Degletagne, Odd Terje Brustugun, Vincent Cahais, Giovanni Centonze, Amélie Chabrier, Cyrille Cuenin, Francesca Damiola, Vincent Thomas de Montpréville, Jean-François Deleuze, Anne-Marie C Dingemans, Élie Fadel, Nicolas Gadot, Akram Ghantous, Paolo Graziano, Paul Hofman, Véronique Hofman, Alejandro Ibáñez-Costa, Stéphanie Lacomme, Nuria Lopez-Bigas, Marius Lund-Iversen, Massimo Milione, Lucia Anna Muscarella, Sergio Pedraza-Arevalo, Corinne Perrin, Gaetane Planchard, Helmut Popper, Luca Roz, Angelo Sparaneo, Wieneke Buikhuisen, José van den Berg, Margot Tesselaar, Jaehee Kim, Ernst Jan M Speel, Séverine Tabone-Eglinger, Thomas Walter, Gavin M Wright, Justo P Castaño, Lara Chalabreysse, Liming Chen, Christophe Caux, Marco Volante, Nicolas Girard, Jean-Michel Vignaud, Esther Conde, Audrey Mansuet-Lupo, Luka Brcic, Giuseppe Pelosi, Mauro Giulio Papotti, Sylvie Lantuejoul, Jules Derks, Talya Dayton, Nicolas Alcala, Matthieu Foll, Lynnette Fernandez-Cuesta","doi":"10.1186/s12943-026-02721-7","DOIUrl":"10.1186/s12943-026-02721-7","url":null,"abstract":"<p><strong>Background: </strong>Lung neuroendocrine tumours (NETs, also known as carcinoids) are rapidly rising in incidence worldwide but have unknown aetiology and limited therapeutic options beyond surgery. The current WHO classification, based on mitotic count and presence or absence of necrosis, divides lung NETs into grade-1 typical, and grade-2 atypical tumours. This dichotomous classification however does not account for recently described molecular entities nor is it sufficient for clinical management.</p><p><strong>Methods: </strong>Here we conducted integrative multi-omic analyses on over 300 lung NETs including whole-genome sequencing, transcriptome profiling, and DNA methylation arrays, followed by archetype analysis, to identify and characterise molecular groups. We further investigated molecular groups using spatial RNA sequencing and proteomics, and deep learning analysis of whole slide images.</p><p><strong>Results: </strong>The integration of multi-omic data provided definitive proof of the existence of four strikingly different molecular groups that vary in patient characteristics, genomic and transcriptomic profiles, microenvironment, and morphology. Among these, we identified a new molecular group, enriched for highly aggressive supra-carcinoids that displayed an immune-rich microenvironment linked to tumour-macrophage crosstalk. We uncovered an undifferentiated cell population within supra-carcinoids and show the transcriptomic similarities between supra-carcinoids and the recently identified atypical small cell lung cancer tumours, further demonstrating their molecular link to high-grade lung neuroendocrine carcinomas. Multi-regional genomic analyses identified distinct evolutionary trajectories, suggesting that molecular groups are determined early in tumourigenesis by genomic events, and that transitions between groups, though infrequent, are possible for supra-carcinoids. Deep learning models accurately identified these groups based on morphology alone, outperforming current histological criteria. Together with the validation of a panel of immunohistochemistry markers, we demonstrated that these molecular groups can be accurately identified based on morphological features, facilitating their future implementation in the clinical setting. Our proposed morpho-molecular classification highlights potential group-specific therapeutic opportunities, with differences in expression to DLL3, EGFR, FGFR and TERT inhibitor targets.</p><p><strong>Conclusions: </strong>Overall, our findings unify previously proposed molecular classifications and refine the lung cancer map by revealing novel tumour phenotypes with potential implications for prognosis and therapeutic management.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830803","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":"Correction: Novel lncRNA-IUR suppresses Bcr-Abl-induced tumorigenesis through regulation of STAT5-CD71 pathway.","authors":"Xuefei Wang, Jianling Yang, Guijie Guo, Riyue Feng, Ke Chen, Yuan Liao, Lianfeng Zhang, Liping Sun, Shile Huang, Ji-Long Chen","doi":"10.1186/s12943-026-02776-6","DOIUrl":"10.1186/s12943-026-02776-6","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830675","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":"Programmable ZBTB7A RNA N⁶-methyladenosine site-specific demethylation suppresses colorectal cancer liver metastasis.","authors":"Xuena Chen, Shuo Zhao, Bochen Liu, Yujia Fan, Huanlu Qiu, Lingtong Ren, Xinrui Zhang, Shurui Yan, Yachun An, Shirong Li, Jie An, Jinshen Wang, Huili Hu","doi":"10.1186/s12943-026-02772-w","DOIUrl":"10.1186/s12943-026-02772-w","url":null,"abstract":"<p><p>Colorectal cancer liver metastasis (CRLM) is the primary cause of CRC-related mortality, with inevitable chemoresistance to targeted therapies and immunotherapy. N⁶-methyladenosine (m⁶A), as a crucial epigenetic regulator of gene expression and cellular physiology, involved in the pathogenesis of CRLM. Precise manipulation of m⁶A modifications could offer a non-pharmacological precision treatment for many diseases. However, the precise editing of m⁶A modification in regulating CRLM progression remains elusive. Here we integrated multi-omics and identified zinc finger and BTB domain-containing 7A (ZBTB7A) as an m⁶A-modified transcription factor that promoted CRLM. Mechanistically, METTL3-mediated m⁶A modification of ZBTB7A facilitated recognition by the m⁶A reader YTHDF1/3 complex, enhancing its translation and expression. This m⁶A-dependent regulation promoted CRLM progression via activation of the ARHGAP26/Rho GTPase signaling axis. Notably, we applied a targeted RNA m⁶A erasure (TRME) system to achieve site-specific demethylation at a single site (m⁶A_site_411666) within ZBTB7A mRNA, without perturbing m⁶A abundance. Temporal demethylation at this site is sufficient to inhibit the CRC cell migration. This study unveils the critical role of the METTL3/ZBTB7A/ARHGAP26 axis in the process of m⁶A-mediated CRLM and positions m⁶A precise editing as a promising therapy in the preclinical treatment of CRLM.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830841","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":"Editorial expression of concern: Epigenetic reactivation of estrogen receptor-α (ERα) by genistein enhances hormonal therapy sensitivity in ERα-negative breast cancer.","authors":"Yuanyuan Li, Syed M Meeran, Shweta N Patel, Huaping Chen, Tabitha M Hardy, Trygve O Tollefsbol","doi":"10.1186/s12943-026-02720-8","DOIUrl":"10.1186/s12943-026-02720-8","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701758","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":"Advances in improving cancer immunotherapy with nanotechnology: from smart nanoparticles to synergistic combination strategies.","authors":"Untack Cho, Jingjing Pu, Amit Sharma, Junhyuk Song, Ji Hyeon You, Yona Kim, Pyung Won Im, Hyung Woo Park, Hyo Eun Moon, Ho Sung Myeong, Hye Ran Park, Jian Hou, Ingo G H Schmidt-Wolf, Sun Ha Paek","doi":"10.1186/s12943-026-02736-0","DOIUrl":"10.1186/s12943-026-02736-0","url":null,"abstract":"<p><p>Cancer immunotherapy has substantially advanced cancer treatment, achieving durable responses in select malignancies. However, its widespread application is limited by significant challenges: low efficacy in many solid tumors, severe side effects, and immune evasion facilitated by the tumor microenvironment (TME). Nanotechnology offers a promising approach to address these obstacles. By employing nanoparticles (NPs), we can precisely deliver therapeutics to tumor sites, ensure controlled release to minimize side effects, and amplify the immune response, thereby substantially boosting the effectiveness of immunotherapy. This review comprehensively highlights the latest advancements in using nanotechnology to enhance cancer immunotherapy. This paper details various applications of nanotech in this field. It discusses smart nanoparticles that respond to TME signals to release drugs (e.g., checkpoint inhibitors) directly at the tumor, reducing systemic side effects and activating T-cells. We also explore how nanovaccines, which co-deliver tumor markers and immune boosters, can induce antigen-specific immune responses. Furthermore, mRNA-loaded nanoparticles can directly modify CAR T-cells inside the body, simplifying treatment and increasing efficacy. Strategies like using PLGA NPs to deliver immune enhancers such as IL-2 are also presented, which activate immune cells while minimizing systemic issues. The review also explains how nanoparticles can re-engineer the immunosuppressive TME to create an environment more conducive to immune action. We also emphasize that nanotechnology-enhanced adoptive therapies, particularly cytokine-induced killer (CIK) cell immunotherapy, hold great potential to improve tumor targeting, treatment persistence durability, and overall anticancer efficacy. Collectively, we highlight synergistic effects achieved by combining nanoparticles with other treatments like chemotherapy, radiation, photothermal/photodynamic therapy, and more, which can turn hard-to-treat tumors into susceptible targets. The integration of nanotechnology and immunotherapy holds the potential to meaningfully advance future cancer therapy.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13419314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620840","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":"Radiotherapy and tertiary lymphoid structures: balancing immune activation and immune damage in cancer immunotherapy.","authors":"Yi Zhang, Hongshuai Li, Siyao Lv, Wenjun Meng, Jiamin Guo, Yating Lu, Lina Peng, Wu Chen, Wen Yang, Xingchen Peng","doi":"10.1186/s12943-026-02735-1","DOIUrl":"https://doi.org/10.1186/s12943-026-02735-1","url":null,"abstract":"<p><p>Cancer immunotherapy, exemplified by immune checkpoint blockade (ICB), remains strongly influenced by the pre-existing immune organization of the tumor microenvironment. Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates whose density, maturation state, and spatial localization correlate with clinical prognosis and ICB response across several malignancies. Radiotherapy (RT) can reshape this immune context in opposing directions. By inducing immunogenic cell death, antigen release, cGAS-STING/type I interferon signaling, vascular remodeling, and lymphocyte recruitment, RT can create conditions that support TLS-associated antitumor immunity in selected settings. Conversely, high-dose or large-volume irradiation, poorly timed nodal exposure, and collateral injury to lymphocytes, tumor-draining lymph nodes, stromal scaffolds, and high endothelial venules can disrupt established TLSs or prevent their maturation. This review summarizes current evidence on the bidirectional relationship between RT and TLS biology, differentiating validated mechanisms from indirect evidence and hypothesis-generating translational concepts. We expound on how dose, fractionation, timing, irradiated volume, nodal management and radiation modality may influence antigen presentation, lymphocyte availability, and local immune architecture. Potential strategies such as lymph-node-aware planning, proton or heavy-ion therapy, FLASH RT, vascular normalization, STING or LTβR agonism, and ICB combinations are evaluated as investigational approaches rather than established TLS-directed clinical interventions. Future studies should evaluate whether optimized RT regimens can preserve or promote the functional maturation of TLSs, integrating paired tissue biopsies, spatial transcriptomics, advanced imaging, and circulating biomarkers to definitively correlate TLS remodeling with clinical outcomes.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":" ","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550120","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":"Spatial proteomics reveals four-stage molecular evolution in cancer immunotherapy-related gastritis.","authors":"Lei Shi, Zhongqiao Lin, Huishan Zhang, Yuping Lu, Zequn Sun, Bin Lan, Huang Xia, Shuimei Luo, Ling Chen, Zhida Wu, Yuyang Huang, Mengru Quan, Xuefeng Wang, Jing Lin, Yu Chen","doi":"10.1186/s12943-026-02737-z","DOIUrl":"https://doi.org/10.1186/s12943-026-02737-z","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, yet immune-related adverse events (irAEs) including immunotherapy-related gastritis (IRAEG) pose significant clinical challenges-often necessitating treatment interruption that may compromise antitumor efficacy. IRAEG presents with atypical symptoms, lacks specific biomarkers, and shows histopathological overlap with other forms of gastritis, complicating diagnosis and management. Despite increasing clinical recognition, a systematic understanding of spatial molecular alterations across the full disease course remains limited. Here, we used spatial proteomics to map the molecular landscape of IRAEG during disease progression and to define stage-specific patterns of molecular evolution relevant to cancer immunotherapy management.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We analyzed tissue samples from seven patients, including four non-immunotherapy-related gastritis controls and three cancer patients who developed IRAEG following ICI therapy for solid tumors, sampled longitudinally across four disease stages: baseline (G1), acute severe inflammation (G2), early recovery (G3), and complete recovery (G4). Using laser capture microdissection coupled with data-independent acquisition mass spectrometry, we profiled 177 spatially resolved gastric tissue regions. Multiplex immunohistochemistry and immunofluorescence characterized features of the immune microenvironment, while Gene Ontology, KEGG pathway analysis, Gene Set Variation Analysis, and xCell inference enabled functional, metabolic, and immune profiling. Key immune and NET-related findings were further validated by multiplex immunofluorescence in an independent, expanded cohort of IRAEG and non-immunotherapy-related gastritis samples.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;IRAEG was characterized by widespread HLA molecule activation and enhanced antigen processing, resembling the immune phenotype observed in organ transplant rejection. The acute G2 stage exhibited excessive neutrophil extracellular trap formation, profound metabolic suppression, and collapse of immune homeostasis-features that may inform early intervention strategies to preserve ICI treatment continuity. During early recovery (G3), inflammatory injury transitioned toward repair, marked by activation of fatty acid metabolism and PPAR signaling. Notably, even at complete clinical recovery (G4), more than 1,000 proteins remained differentially expressed, reflecting sustained enhancement of metabolic and immune functions and establishing a distinct molecular \"memory\" state with implications for ICI rechallenge decisions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;These findings define four molecularly distinct stages of IRAEG progression and recovery. The stage-specific signatures identified here serve as candidate biomarkers for diagnosis, disease staging, and therapeutic response assessment, and may guide clinical decisions regarding irAE management,","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":" ","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550094","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}