Nature cancer最新文献

{"title":"Next-generation cancer therapeutics","authors":"","doi":"10.1038/s43018-026-01244-w","DOIUrl":"10.1038/s43018-026-01244-w","url":null,"abstract":"Cancer therapies have evolved substantially in recent decades; however, there remains a pressing need for new therapeutic options. Our Series on Next-Generation Cancer Therapeutics presents commissioned Reviews and opinion pieces on the latest therapeutic approaches and their implementation in the existing clinical landscape.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 9","pages":"1325-1325"},"PeriodicalIF":28.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-026-01244-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023279","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":"An iron-regulated methionine redox axis governs adipose browning and cancer cachexia.","authors":"Jung Seung Nam, Sung Shin Ahn, Yeonoh Shin, Ariana Vargas-Castillo, Maya S Dixon, Pardis Ahmadi, Kathrin Schilling, Fereshteh Zandkarimi, Alex Chen, Nal Ae Yoon, Harrison Cullen, Yanping Sun, Thomas C Caffrey, Kelsey A Klute, Benjamin J Swanson, Jordan Lu, Samuel Pan, Yuxuan Chen, Shu Ichimiya, Geena Kim, Jeanine M Genkinger, Kazuki Sugahara, Michael D Kluger, Paul Grandgenett, Michael A Hollingsworth, Luke Berchowitz, Anthony W Ferrante, Lori M Zeltser, Sabrina Diano, Iok In Christine Chio","doi":"10.1038/s43018-026-01234-y","DOIUrl":"10.1038/s43018-026-01234-y","url":null,"abstract":"<p><p>Adipose browning and atrophy are early events of cachexia, a lethal metabolic disorder affecting nearly half of the population with cancer. Here, using individual-derived specimens and mouse models, we identified an iron-dependent pathway that initiates adipose browning in both physiological and cachectic settings. Upon adrenergic stimulation of adipocytes, an influx of iron induces the activity of methionine sulfoxide reductase A (MSRA), an enzyme that reverses the oxidation of proteinaceous methionine residues. Mechanistically, iron coordination by the conserved iron-binding EXXH motif of two MSRA polypeptides serves to dimerize, stabilize and elevate its reductase activity. Iron-bound MSRA dimers in turn promote adipose browning by maintaining the reduced state of select substrates, including the catalytic subunit of protein kinase A. Remarkably, in mouse models, MsrA deletion impairs adipose browning, mitigates cachexia and prolongs the survival of tumor-bearing animals. Thus, as a key nexus of cancer-associated cachexia, the β3 adrenergic receptor-iron-MSRA axis is a promising target for clinical intervention.</p>","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":28.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025543","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":"Adipocyte methionine reduction promotes cancer cachexia.","authors":"Stefan Offermanns","doi":"10.1038/s43018-026-01202-6","DOIUrl":"10.1038/s43018-026-01202-6","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":28.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025524","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":"A universal visual foundation model for computational cytopathology.","authors":"Xueyi Zheng, Ke Zheng, Jue Wang, Xinke Zhang, Kai Li, Zihan Zhao, Chaofeng Li, Haohua Chen, Ruixuan Wang, Junpeng Lai, Bing Chu, Sha Fu, Dan Xie, Muyan Cai","doi":"10.1038/s43018-026-01240-0","DOIUrl":"10.1038/s43018-026-01240-0","url":null,"abstract":"<p><p>Cytopathology is central to cancer screening and diagnosis but remains labor-intensive, motivating the development of scalable computational solutions. Here, we present CROWN (Cytology visual foundation netwoRk Optimized With self-supervised learNing), a universal visual foundation model for computational cytopathology. CROWN was pretrained on more than 10 million cytology image patches using a DINOv2-based self-supervised framework, without requiring manual annotations during pretraining. We evaluated CROWN in 202 task-setting combinations spanning classification, segmentation, detection, retrieval and slide-level prediction across private institutional cohorts and public datasets. CROWN achieved the best overall performance among established pretrained encoders across diverse benchmark settings, with accuracy exceeding 95% in 48 patch-level classification evaluations and 98% in 22 of them. These findings support CROWN as a scalable visual backbone for general-purpose computational cytopathology across heterogeneous datasets and task settings.</p>","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":28.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002398","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":"Local antibody-driven response to anti-PD-1 blockade","authors":"Heathcliff Dorado García","doi":"10.1038/s43018-026-01246-8","DOIUrl":"10.1038/s43018-026-01246-8","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 9","pages":"1327-1327"},"PeriodicalIF":28.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982760","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":"Engineering botulinum neurotoxin into anti-cancer agents","authors":"Julieta Afonso","doi":"10.1038/s43018-026-01245-9","DOIUrl":"10.1038/s43018-026-01245-9","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 9","pages":"1326-1326"},"PeriodicalIF":28.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976833","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":"Circulating tumor DNA-guided de-escalation or escalation of adjuvant therapy in high-risk stage II and stage III colon cancer: the phase 2 PEGASUS trial.","authors":"Silvia Marsoni, Clara Montagut, Filippo Pietrantonio, Andrea Sartore-Bianchi, Luca Lazzari, Francesca Bergamo, Maria Giulia Zampino, Noelia Tarazona, Mario Mandalà, Stefano Tamberi, Elena Elez, Cristina Santos Vivas, Paolo Luraghi, Michele Prisciandaro, Federica Tosi, Davide Ciardiello, Joana Vidal, Victor Seguì, Michele Palazzo, Giulia Maddalena, Katia Bencardino, Ida Taglialatela, Marta Guix, Eliana Rulli, Valentina Vettore, Federica Morano, Claudio Isella, Giovanni Crisafulli, Giorgio Patelli, Enzo Medico, Alberto Bardelli, Andrés Cervantes, Valter Torri, Josep Tabernero, Salvatore Siena, Sara Lonardi","doi":"10.1038/s43018-026-01237-9","DOIUrl":"https://doi.org/10.1038/s43018-026-01237-9","url":null,"abstract":"<p><p>Oxaliplatin-fluoropyrimidine combinations are standard adjuvant therapy after radical resection of high-risk stage II and stage III colon cancer but expose many patients to toxicity while failing to prevent relapse in others. PEGASUS was a multicenter, single-arm, phase 2 trial evaluating the feasibility of an adaptive circulating tumor DNA (ctDNA)-guided treatment strategy in patients with resected microsatellite-stable, T4N0 or stage III colon cancer. Postsurgery ctDNA-positive patients received 3 months of CAPOX, escalating to 6 months of FOLFIRI if persistently positive, whereas confirmed ctDNA-negative patients received 6 months of capecitabine. The primary endpoint was the 2-year relapse-free rate among ctDNA-negative patients at 2 subsequent postsurgery liquid biopsies. Among the 135 enrolled patients, 26% (n = 35) were ctDNA positive at the postsurgery landmark, with a 3-year disease-free survival rate of 58% for ctDNA positive versus 83% for ctDNA negative (hazard ratio = 2.71; 95% CI = 1.35-5.45; P = 0.0036). With 100 rather than 134 ctDNA-negative cases, the observed 2-year relapse-free rate (88%, 90% CI = 81-93%) was below the predefined threshold (≥92%); the primary endpoint was not met. Versus a matched TOSCA ( NCT00646607 ) control cohort, ctDNA-guided strategy showed similar disease-free survival and substantially less neurotoxicity. Transcriptomic profiling linked the relapse to consensus molecular subtype 4, stroma-rich biology. These findings suggest that dynamic ctDNA-guided management can be leveraged operationally in clinical practice, highlighting the needs for randomized trials and more effective strategies for ctDNA-positive disease. ClinicalTrials.gov identifier: NCT04259944 .</p>","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":28.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970194","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":"Targeting valine metabolism and ferroptosis to overcome chemoresistance in PDAC.","authors":"","doi":"10.1038/s43018-026-01235-x","DOIUrl":"https://doi.org/10.1038/s43018-026-01235-x","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":28.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970177","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":"MMSDH facilitates ACSL4 propionylation to counteract ferroptosis upon hypoxia and impairs PDAC chemotherapy efficacy.","authors":"Peixiang Zheng, Yanni Lin, Meiyin Zhang, Zhiyuan Tang, Wenxing Qin, Min Xiao, Xue Sun, Yuli Shen, Zhiqiang Hu, Shuo Ru, Yuran Duan, Bofei Dong, Ting Wen, Mengdie Li, Hong Wu, Yueru Hou, Guimei Ji, Zheng Wang, Xiaohong Wu, Qimin Zhou, Xiaoguang Liu, Gaopeng Li, Yuhao Wang, Shengzhong Duan, Yang Luo, Bo Chu, Xu Qian, Zhimin Lu, Yuan Ding, Chuan Xu, Xu Qian, Tong Liu, Daqian Xu","doi":"10.1038/s43018-026-01236-w","DOIUrl":"10.1038/s43018-026-01236-w","url":null,"abstract":"<p><p>Limited efficacy of neoadjuvant chemotherapy (NAC) in pancreatic ductal adenocarcinoma (PDAC) underscores the need for novel combination strategies and a deeper understanding of metabolic determinants of chemoresistance. Here we identify methylmalonate semialdehyde dehydrogenase (MMSDH), a valine catabolism enzyme, as a driver of gemcitabine (GC) resistance. Hypoxia induces GCN5-mediated lactylation of MMSDH at K113. Lactylated MMSDH interacts with acyl-CoA synthetase long-chain family member 4 (ACSL4), generating propionyl-CoA to facilitate KAT8-mediated ACSL4 K606 propionylation. This modification enhances ACSL4-HSC70 binding, promoting its degradation through chaperone-mediated autophagy. Critically, this MMSDH-mediated ACSL4 propionylation correlates with low ACSL4 levels and poor NAC response in recipients. Combining dietary valine restriction with GC synergistically induces ferroptosis and suppresses tumor growth. Blocking MMSDH-K113la disrupts this axis, potentiating GC-induced ferroptosis and inhibiting tumor progression. These findings reveal a previously unknown mechanism of ferroptosis evasion through valine metabolism and ACSL4 regulation, nominating the GCN5-MMSDH-ACSL4 axis as a therapeutic target to enhance PDAC chemosensitivity.</p>","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":28.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956365","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":"Commensal Nakaseomyces glabratus migrates into prostate tumors to accelerate cancer progression.","authors":"Ping Lai, Lei Liu, Nicolò Pernigoni, Yingxi Du, Daniele Braga, Martina Troiani, Giuseppe Attanasio, Yuxin Li, Pan Song, Emiliano Pasquini, Tanja Rezzonico Jost, Xiaowen Huang, Martino Maddalena, Simone Mosole, Andrea Rinaldi, Giovanna Pecoraro, Martino Pedrani, Aurora Valdata, Nicolò Bancaro, Luisa Maraccani, Alessandra De Giani, Wei Yuan, Lewis Gallagher, Khobe Chandran, Penny Flohr, Pasquale Rescigno, Giuseppe Reitano, Alessandro Morlacco, Fabrizio Dal Moro, Isabella Giacomini, Monica Montopoli, Matteo Brunelli, Serena Pedron, Ricardo Pereira Mestre, Raad Z Gharaibeh, Christian Jobin, Silke Gillessen Sommer, Johann de Bono, Andrea Alimonti","doi":"10.1038/s43018-026-01229-9","DOIUrl":"https://doi.org/10.1038/s43018-026-01229-9","url":null,"abstract":"<p><p>Recent studies demonstrate that the gut mycobiota plays a key role in several tumors. However, the contribution of commensal fungi to prostate cancer initiation and progression remains understudied. Here we find that Nakaseomyces glabratus is enriched in fecal, blood and tumor samples of patients with castration-resistant prostate cancer, correlating with patients' poor overall survival. Oral administration of N. glabratus to castrated mice accelerated cancer progression by promoting infiltration and activation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, androgen deprivation therapy increases intestinal permeability, resulting in the leakage of N. glabratus from the gut to the tumor site, activating PMN-MDSCs via the Dectin-2 receptor. Treatment of mice with a negatively charged intestinal hydrogel blocks N. glabratus translocation to tumor, reducing PMN-MDSCs' intratumoral infiltration and activation. Taken together, these findings reveal that the gut-to-tumor translocation of N. glabratus contributes to endocrine resistance in prostate cancer by enhancing the immunosuppressive microenvironment of these tumors.</p>","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":28.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920356","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}