Cancer discovery最新文献

Shared-Antigen Cancer Vaccines Keep Falling Short 共享抗原癌症疫苗供不应求

IF 28.2 1区医学

Cancer discovery Pub Date : 2026-10-20 DOI: 10.1158/2159-8290.cd-nw2026-0096

引用次数: 0

Domain Shuffling Builds Synthetic Genes that Boost CAR T-Cell Design. 区域洗牌构建促进CAR - t细胞设计的合成基因。

IF 29.5 1区医学

Cancer discovery Pub Date : 2026-10-20 DOI: 10.1158/2159-8290.CD-RW2026-093

引用次数: 0

H3K4me1-Mediated Epigenomic Priming of Chemoresistant Tumor States in Ovarian Cancer h3k4me1介导的卵巢癌耐药肿瘤状态的表观基因组启动

IF 28.2 1区医学

Cancer discovery Pub Date : 2026-10-19 DOI: 10.1158/2159-8290.cd-26-0180

Yuna Landais, Juliette Bertorello, Marta Plasencia Puerto, Agathe Kahn, Baptiste Simon, Amélie Roehrig, Adeline Durand, Marceau Quatredeniers, Constance Lamy, Enora Laas, Nicolas Pouget, Simon Dumas, Jean-Guillaume Féron, Virginie Fourchotte, Claire Bonneau, Vincent Cockenpot, Marianne Delville, Magali Richard, Maud Kamal, Fabrice Lecuru, Christophe Le Tourneau, Céline Vallot

{"title":"H3K4me1-Mediated Epigenomic Priming of Chemoresistant Tumor States in Ovarian Cancer","authors":"Yuna Landais, Juliette Bertorello, Marta Plasencia Puerto, Agathe Kahn, Baptiste Simon, Amélie Roehrig, Adeline Durand, Marceau Quatredeniers, Constance Lamy, Enora Laas, Nicolas Pouget, Simon Dumas, Jean-Guillaume Féron, Virginie Fourchotte, Claire Bonneau, Vincent Cockenpot, Marianne Delville, Magali Richard, Maud Kamal, Fabrice Lecuru, Christophe Le Tourneau, Céline Vallot","doi":"10.1158/2159-8290.cd-26-0180","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-26-0180","url":null,"abstract":"Non-genetic intratumor heterogeneity underlies therapeutic failure in cancer, yet how resistant tumor states are encoded in patients remains unclear. In this study, we show that chemoresistant evolution in high-grade serous ovarian cancer (HGSOC) is prefigured by epigenetically primed tumor cell states present before therapy. Using multimodal single-nucleus approaches, we profile transcriptional programs and histone modifications from longitudinal frozen biopsies of 16 patients with HGSOC. Tumors comprise a limited set of functional states that evolve reproducibly under chemotherapy: proliferative and IFN-responsive states are depleted, whereas TNFα-associated and epithelial-mesenchymal transition–associated programs persist or expand. Chromatin profiling reveals that these resistant programs are broadly enriched for histone H3 lysine 4 monomethylation (H3K4me1) prior to treatment, indicating that features of resistance are epigenomically primed. Baseline tumor composition is associated with survival, and fibroblast remodeling accompanies malignant adaptation. Together, these findings identify epigenomic priming as a feature of chemoresistant tumor cell states and provide a scalable framework for anticipating resistance from biopsies. Significance: Using a clinically compatible multimodal single-nucleus approach, the authors show that chemoresistant evolution in HGSOC is prefigured by epigenetically primed tumor cell states present before therapy.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"37 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218452","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

Cabergoline Suppresses Postpartum Breast Cancer by Enhancing Mammary Gland Involution in Brca1-Mutant Mice and Is Associated with Reduced Risk in Younger Women 卡麦角林通过增强brca1突变小鼠的乳腺退化来抑制产后乳腺癌，并与降低年轻女性的风险相关

IF 28.2 1区医学

Cancer discovery Pub Date : 2026-10-15 DOI: 10.1158/2159-8290.cd-26-0187

Natalia García-Sancha, Roberto Corchado-Cobos, Ryan Ghorayeb, Adrián Blanco-Gómez, Oriol Cunillera, Diego Alonso-López, Nathalie C. Støer, Francesca Mateo, Roderic Espín, Le Tam Nhan Nguyen, Mercè Marzo-Castillejo, Chelsey L. Gough, Katy Milne, Sonia Castillo-Lluva, Javier De las Rivas, Julio Pozo, Alberto Orfao, Luis Palomero, Jaime Pignatelli, Eva Sacristan-Horcajada, Luis Félix. Valero-Juan, Carmen Patino-Alonso, David Perera, Ashok R. Venkitaraman, Jian-Hua Mao, Hang Chang, Alejandro Jiménez-Navas, Manuel Jesús Pérez-Baena, Nélida Salvador, Marina Mendiburu-Eliçabe, Patricia Gonzalez-Garcia, Eduardo Caleiras, Isabel Peset, María Begoña García-Cenador, Francisco Javier. Garcia-Criado, Brad H. Nelson, Edoardo Botteri, Miquel Angel. Pujana, Christopher A. Maxwell, Jesús Pérez-Losada

{"title":"Cabergoline Suppresses Postpartum Breast Cancer by Enhancing Mammary Gland Involution in Brca1-Mutant Mice and Is Associated with Reduced Risk in Younger Women","authors":"Natalia García-Sancha, Roberto Corchado-Cobos, Ryan Ghorayeb, Adrián Blanco-Gómez, Oriol Cunillera, Diego Alonso-López, Nathalie C. Støer, Francesca Mateo, Roderic Espín, Le Tam Nhan Nguyen, Mercè Marzo-Castillejo, Chelsey L. Gough, Katy Milne, Sonia Castillo-Lluva, Javier De las Rivas, Julio Pozo, Alberto Orfao, Luis Palomero, Jaime Pignatelli, Eva Sacristan-Horcajada, Luis Félix. Valero-Juan, Carmen Patino-Alonso, David Perera, Ashok R. Venkitaraman, Jian-Hua Mao, Hang Chang, Alejandro Jiménez-Navas, Manuel Jesús Pérez-Baena, Nélida Salvador, Marina Mendiburu-Eliçabe, Patricia Gonzalez-Garcia, Eduardo Caleiras, Isabel Peset, María Begoña García-Cenador, Francisco Javier. Garcia-Criado, Brad H. Nelson, Edoardo Botteri, Miquel Angel. Pujana, Christopher A. Maxwell, Jesús Pérez-Losada","doi":"10.1158/2159-8290.cd-26-0187","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-26-0187","url":null,"abstract":"Breast cancer that arises in the postpartum period often carries a poor prognosis and urgently requires chemoprevention strategies, particularly for women at elevated risk. Here, we report that a single post-lactation dose of cabergoline, a dopaminergic agonist that blocks prolactin secretion, delays the onset and reduces the incidence of postpartum mammary cancer in K14-Cre; Brca1F/F, Trp53F/F mice. In these mice, cabergoline treatment remodels the mammary gland by potentiating involution, reducing ductal area and proliferation, and reversing T cell exhaustion, potentially through modulation of ion channel expression. Notably, independent retrospective studies in two large cohorts of European women showed that cabergoline treatment was associated with a lower incidence of postpartum breast cancer, with a meta-analysis indicating an approximate 69% reduction in risk. Our work underscores the importance of targeting postlactational involution as a strategy for the prevention of postpartum breast cancer and positions cabergoline as a novel, low-risk chemoprevention strategy.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"293 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172865","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

Binding-To-Release Enhances Efficacy of Small Molecule-Drug Conjugates. 结合释放增强小分子药物偶联物的疗效。

IF 29.5 1区医学

Cancer discovery Pub Date : 2026-10-15 DOI: 10.1158/2159-8290.CD-RW2026-092

引用次数: 0

Two New Federal Efforts Designed to Accelerate Clinical Trials 两项新的联邦努力旨在加速临床试验

IF 28.2 1区医学

Cancer discovery Pub Date : 2026-10-14 DOI: 10.1158/2159-8290.cd-nw2026-0095

引用次数: 0

Mutability Dependence of Breast Cancer Metastasis and Latency to Recurrence 乳腺癌转移和复发潜伏期的易变性依赖性

IF 28.2 1区医学

Cancer discovery Pub Date : 2026-10-13 DOI: 10.1158/2159-8290.cd-25-2090

Matthew R. Lawrence-Paul, Tien-chi Pan, Dhruv K. Pant, Natalie N.C. Shih, Yan Chen, George K. Belka, Igor Makhlin, Christina Curtis, Angela M. DeMichele, Lewis A. Chodosh

{"title":"Mutability Dependence of Breast Cancer Metastasis and Latency to Recurrence","authors":"Matthew R. Lawrence-Paul, Tien-chi Pan, Dhruv K. Pant, Natalie N.C. Shih, Yan Chen, George K. Belka, Igor Makhlin, Christina Curtis, Angela M. DeMichele, Lewis A. Chodosh","doi":"10.1158/2159-8290.cd-25-2090","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-2090","url":null,"abstract":"To evaluate the functional relevance of mutations newly detected in breast cancer metastases, we analyzed genomic data from 662 paired and ~6,000 unpaired primary and metastatic tumors. These analyses indicate that metastasis-specific mutations are frequently acquired post-dissemination, with a disproportionate contribution from APOBEC-mediated mutagenesis. Metastasis-specific mutations converged on a set of pathways that were highly recurrent, distinct from those altered in primary tumors, and dependent on metastatic site. 95% of patients harbored metastasis-specific mutations within a minimum set of 10 pathways. Remarkably, more than half the variation in metastatic latency across patients was explained by the relative timing of mutation acquisition within implicated pathways before versus after dissemination. These findings support a “mutability-dependent” model of metastasis in which functionally consequential mutations accumulate after primary tumor dissemination and contribute to metastatic outgrowth, with latency reflecting the time required for DTCs to acquire the remaining driver mutations needed to achieve metastatic competence.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"12 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149152549","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

Lean Adipocytes Secrete Lipids that Sensitize Breast Cancer to Ferroptosis. 瘦脂肪细胞分泌脂质使乳腺癌对铁下垂敏感。

IF 29.5 1区医学

Cancer discovery Pub Date : 2026-10-13 DOI: 10.1158/2159-8290.CD-RW2026-091

引用次数: 0

Spatial Proximity Mapping Identifies Vulnerabilities for Therapeutic Co-Targeting. 空间接近映射识别治疗共同靶向的脆弱性。

IF 29.5 1区医学

Cancer discovery Pub Date : 2026-10-08 DOI: 10.1158/2159-8290.CD-RW2026-090

引用次数: 0

Universal Germline Genetic Testing after a Diagnosis of Cancer 癌症诊断后的通用种系基因检测

IF 28.2 1区医学

Cancer discovery Pub Date : 2026-10-08 DOI: 10.1158/2159-8290.cd-26-0971

Zsofia K. Stadler, Anna Maio, Aliya Khurram, Kanika Arora, Chaitanya Bandlamudi, Ying L. Liu, Yelena Kemel, Margaret Sheehan, Erin Salo-Mullen, Angelika Padunan, Tina Alano, William D. Tap, Julia L. Glade Bender, Andrea Cercek, Ingo K. Mellinghoff, Eileen M. O’Reilly, Alan L. Ho, Michael D. Offin, Alexander N. Shoushtari, Chimene A. Kesserwan, Mohammad Abbass, Lauren Banaszak, Lisa M. DeAngelis, Yonina R. Murciano-Goroff, Marc Ladanyi, Ozge Ceyhan-Birsoy, Maria I. Carlo, Alicia Latham, Mark E. Robson, David B. Solit, Michael F. Berger, Diana L. Mandelker, Kenneth Offit, Luis A. Diaz

{"title":"Universal Germline Genetic Testing after a Diagnosis of Cancer","authors":"Zsofia K. Stadler, Anna Maio, Aliya Khurram, Kanika Arora, Chaitanya Bandlamudi, Ying L. Liu, Yelena Kemel, Margaret Sheehan, Erin Salo-Mullen, Angelika Padunan, Tina Alano, William D. Tap, Julia L. Glade Bender, Andrea Cercek, Ingo K. Mellinghoff, Eileen M. O’Reilly, Alan L. Ho, Michael D. Offin, Alexander N. Shoushtari, Chimene A. Kesserwan, Mohammad Abbass, Lauren Banaszak, Lisa M. DeAngelis, Yonina R. Murciano-Goroff, Marc Ladanyi, Ozge Ceyhan-Birsoy, Maria I. Carlo, Alicia Latham, Mark E. Robson, David B. Solit, Michael F. Berger, Diana L. Mandelker, Kenneth Offit, Luis A. Diaz","doi":"10.1158/2159-8290.cd-26-0971","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-26-0971","url":null,"abstract":"Age at diagnosis among patients with cancer is a predictor of pathogenic germline variant prevalence, yet age thresholds often misclassify genetic risk. We performed germline sequencing of 39,184 unselected patients with solid malignancies spanning 32 tumor types, interrogating &gt;90 cancer predisposition genes independent of clinical suspicion. Patients were stratified into early-, average-, and late-onset groups based on standard deviations from tumor-specific mean age at diagnosis. Pathogenic variant prevalence inversely correlated with age at diagnosis: 18.4% in early-onset tumors, 15.6% in average-onset tumors, and 12.3% in late-onset tumors (P &lt; 0.001). Variants in high/moderate-penetrance genes accounted for the enrichment in early-onset cases (12.4%, early-onset; 8.9%, average-onset; 5.1%, late-onset; P &lt; 0.001). Restricting hereditary cancer testing to patients diagnosed before age 50, as is typically done, would miss 4,601 pathogenic variant carriers, 72% of all variants detected. These findings support broad-based germline testing beyond conventional age-based criteria, reflecting the burden of hereditary risk even among late-onset cases. Significance: Across 32 solid tumor types in a pan-cancer cohort, we found enrichment of germline pathogenic variants among patients with subtype-specific early-onset cancer. Using age 50 as a testing cutoff misses most patients with inherited predisposition, supporting universal germline genetic testing for all individuals diagnosed with cancer.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"293 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149123631","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