Cancer discovery最新文献

{"title":"Divergent Evolution of Malignant Subclones Maintains a Balance Between Induced Aggressiveness and Intrinsic Drug Resistance in T Cell Cancer","authors":"Terkild B. Buus, Chella Krishna Vadivel, Maria Gluud, Martin R.J. Namini, Ziao Zeng, Signe Hedebo, Menghong Yin, Andreas Willerslev-Olsen, Emil M.H. Pallesen, Lang Yan, Edda P. Blümel, Emma U. Ewing, Sana Ahmad, Lara P. Sorrosal, Carsten Geisler, Charlotte M. Bonefeld, Anders Woetmann, Mads H. Andersen, Tomas Mustelin, Claus Johansen, Marion Wobser, Maria R. Kamstrup, Emmanuella Guenova, Jürgen C. Becker, Sergei B. Koralov, Rikke Bech, Niels Ødum","doi":"10.1158/2159-8290.cd-24-1856","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-24-1856","url":null,"abstract":"Evolution and outgrowth of drug-resistant cancer cells is a common cause of treatment failure. Patients with leukemic cutaneous T-cell lymphoma (L-CTCL) have a poor prognosis due to development of drug-resistance and severe bacterial infections. Here, we show that most L-CTCL patients harbor multiple genetically distinct subclones that express an identical clonal antigen receptor but display distinct phenotypes and functional properties. These co-existing malignant subclones exhibit differences in tissue homing, metabolism, and cytokine expression, and respond differently to extrinsic factors like Staphylococcus (S.)aureus and cancer drugs. Indeed, while S. aureus toxins selectively enhance activation and proliferation of certain subclones, these responsive subclones are also the most intrinsically sensitive to cancer drugs when the stimuli are removed. Consequently, although divergent evolution of malignant subclones drives aggressiveness, adaptability and drug-resistance, by removing extrinsic stimuli and mapping malignant subclones, we can expose inherent vulnerabilities that can be exploited in the treatment of these cancers.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"307 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144290068","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":"Phase Ib basket expansion trial and alternative-schedule dose-escalation study of ATR inhibitor elimusertib in advanced solid tumors with DNA damage response defects","authors":"Timothy A. Yap, David S.P. Tan, Anastasios Stathis, Geoffrey I. Shapiro, Satoru Iwasa, Markus Joerger, Jingsong Zhang, Ruth Plummer, Michael B. Sawyer, Daniel S.W. Tan, Vincent Castonguay, Nashat Y. Gabrail, Nobuaki Matsubara, Gary Wilkinson, Matthias Ludwig, Andreas Schlicker, Yinghui Zhou, Claudia Merz, J. Henry M. Däbritz, Michael Jeffers, Joseph Hreiki, Johann S. de Bono","doi":"10.1158/2159-8290.cd-24-1500","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-24-1500","url":null,"abstract":"In this Phase Ib basket expansion trial and alternative-schedule dose-escalation study, we evaluated the ATR inhibitor elimusertib at 40 mg twice daily (3 days on/4 days off) in 143 patients with advanced cancer with tumor-associated DNA damage response defects, comprising gynecologic (n=45), prostate (n=19), colorectal (n=24), and breast (n=19) cancer, and ATM loss (n=36). An alternative schedule (3 days on/11 days off) was assessed in patients with ATM loss and/or ATM mutations (n=32). Elimusertib-related reversible hematologic toxicities were observed. Objective responses were modest (4.5%), but a disease control rate (DCR) of 49.3% indicated that subpopulations of patients, especially with gynecologic cancers (DCR 59.5%), derived meaningful durable benefit from elimusertib. There was no association between ATM protein loss or ATM alterations and progression-free survival or overall response. Further studies to define optimal predictive biomarkers for ATR inhibitors as monotherapy and in combination are ongoing.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"12 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144290044","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":"Germline-somatic liaison dictates cancer subtype via de novo steroid biosynthesis.","authors":"Paola Gasperini, Alessandro Alaimo, Blerta Stringa, Yoon-Mi Chung, Yari Ciani, Francesca Lorenzin, Giulia Fracassi, Yanis Zekri, Francesco Orlando, Orsetta Quaini, Sebastian Gregoricchio, Gianluca Petris, Antonio Casini, Christopher E Barbieri, Wilbert Zwart, Anna Cereseto, Nima Sharifi, Andrea Lunardi, Francesca Demichelis","doi":"10.1158/2159-8290.CD-24-1904","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-24-1904","url":null,"abstract":"<p><p>The biological mechanisms underlying the cooperation between germline genetic variants and somatic mutations during carcinogenesis are rarely elucidated. Here, characterizing isogenic prostate cancer cell lines, we dissected the interplay between a germline variant at the 7p14.3 locus (rs1376350, G>A) and early recurrent prostate cancer-specific mutation in the Speckle-Type POZ protein (SPOP) gene across human prostate adenocarcinomas. The transcriptomes of multiple edited models pointed to Gli3 and the Hedgehog signaling pathway in a genotype-specific manner, while SPOP mutation and AR stimulation promote Gli3 accumulation in the full-length (FL) transcriptionally active form. This, in turn, triggers the cell-autonomous production of steroids that prostate cancer relies on, in line with the enhanced responsiveness of SPOP-mutated prostate cancer to androgen deprivation therapy. These data demonstrate that germline variants dictate men's prostate cancer somatic evolution and suggest opportunities to jointly model germline-somatic tandems to help untangle the complexity of human cancer.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":""},"PeriodicalIF":29.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282430","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":"Gut microbiota modulation through Akkermansia spp. supplementation increases CAR-T cell potency","authors":"Laura Marcos-Kovandzic, Michele Avagliano, Myriam Ben Khelil, Janesa Srikanthan, Rim ABDALLAH, Valentina Petrocelli, Jessica Rengassamy, Alexia Alfaro, Mathilde Bied, Marine Fidelle, Gladys Ferrere, Romain Daillere, Ahmadreza Arbab, Roula Amine-Hneineh, Arnaud Pages, Peggy Dartigues, Pierre Ly, Sylvain Simon, Sylvere Durand, Adrian Gottschlich, Florent Ginhoux, Camille Bleriot, Peng Liu, Liwei Zhao, Laura Creusot, Nathalie Rolhion, Guido Kroemer, Laurie Menger, Sebastian Kobold, Cristina Castilla-Llorente, Harry Sokol, Stefano Casola, Edoardo Pasolli, Laurence Zitvogel, Camille Bigenwald","doi":"10.1158/2159-8290.cd-24-1230","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-24-1230","url":null,"abstract":"This study investigates the clinical relevance of the gut microbiome at taxonomic and metabolic levels in anti-CD19 CAR-T cell therapy, both in patients and in a preclinical syngeneic tumor model. B cell lymphoma patients treated with CD19-CAR-T cells exhibited profound intestinal dysbiosis, exacerbated after CAR-T infusion. This dysbiosis was characterized by low bacterial richness, low sMAdCAM-1 and loss of Akkermansia species, associated with resistance to therapy. Mechanistically, oral Akkermansia massiliensis supplementation increased CAR-T cell infiltration into bone marrow, inverted the CD4/CD8 CAR-T ratio, favored Tc1 CD8+ T cell polarization and promoted release of tryptophan-derived indole metabolites, leading to better tumor control. The clinical benefit of Akkermansia spp. supplementation was abolished when CAR-T cells were genetically deficient for the indole receptor, aryl hydrocarbon receptor (Ahr). Ahr-agonistic indoles alone failed to replicate the bacterium’s anticancer effects. These findings suggest Akkermansia supplementation could improve CAR-T cell potency in patients with intestinal Akkermansia deficiency.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"23 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268639","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":"Federated deep learning enables cancer subtyping by proteomics.","authors":"Zhaoxiang Cai, Emma L Boys, Zainab Noor, Adel T Aref, Dylan Xavier, Natasha Lucas, Steven G Williams, Jennifer Ms Koh, Rebecca C Poulos, Yangxiu Wu, Michael Dausmann, Karen L MacKenzie, Adriana Aguilar-Mahecha, Carolina Armengol, Maria M Barranco, Mark Basik, Elise D Bowman, Roderick Clifton-Bligh, Elizabeth A Connolly, Wendy A Cooper, Bhavik Dalal, Anna DeFazio, Martin Filipits, Peter J Flynn, J Dinny Graham, Jacob George, Anthony J Gill, Michael Gnant, Rosemary Habib, Curtis C Harris, Kate Harvey, Lisa G Horvath, Christopher Jackson, Maija R J Kohonen-Corish, Elgene Lim, Jia Jenny Liu, Georgina V Long, Reginald V Lord, Graham J Mann, Geoffrey W McCaughan, Lucy Morgan, Leigh Murphy, Sumanth Nagabushan, Adnan Nagrial, Jordi Navinés, Benedict J Panizza, Jaswinder S Samra, Richard A Scolyer, John Souglakos, Alexander Swarbrick, David Thomas, Rosemary L Balleine, Peter G Hains, Phillip J Robinson, Qing Zhong, Roger R Reddel","doi":"10.1158/2159-8290.CD-24-1488","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-24-1488","url":null,"abstract":"<p><p>Artificial intelligence applications in biomedicine face major challenges from data privacy requirements. To address this issue for clinically annotated tissue proteomic data, we developed a Federated Deep Learning (FDL) approach (ProCanFDL), training local models on simulated sites containing data from a pan-cancer cohort (n=1,260) and 29 cohorts held behind private firewalls (n=6,265), representing 19,930 replicate data-independent acquisition mass spectrometry (DIA-MS) runs. Local parameter updates were aggregated to build the global model, achieving a 43% performance gain on the hold-out test set (n=625) in 14 cancer subtyping tasks compared to local models, and matching centralized model performance. The approach's generalizability was demonstrated by retraining the global model with data from two external DIA-MS cohorts (n=55) and eight acquired by tandem mass tag (TMT) proteomics (n=832). ProCanFDL presents a solution for internationally collaborative machine learning initiatives using proteomic data, e.g., for discovering predictive biomarkers or treatment targets, while maintaining data privacy.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":""},"PeriodicalIF":29.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246593","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":"Aged and BRCA-Mutated Stromal Cells Drive Epithelial Cell Transformation.","authors":"Geyon L Garcia, Taylor Orellana, Grace Gorecki, Leonard Frisbie, Roja Baruwal, Swathi Suresh, Ester Goldfeld, Ian Beddows, Ian P MacFawn, Ananya K Britt, Macy M Hale, Amal Taher Elhaw, Brian R Isett, Nadine Hempel, Riyue Bao, Hui Shen, Ronald J Buckanovich, Toren Finkel, Ronny Drapkin, T Rinda Soong, Tullia C Bruno, Huda I Atiya, Lan G Coffman","doi":"10.1158/2159-8290.CD-24-0805","DOIUrl":"10.1158/2159-8290.CD-24-0805","url":null,"abstract":"<p><p>The fundamental steps in high-grade serous ovarian cancer (HGSOC) initiation are unclear, presenting critical barriers to the prevention and early detection of this deadly disease. Current models propose that fallopian tube epithelial (FTE) cells transform into serous tubal intraepithelial carcinoma (STIC) precursor lesions and subsequently into HGSOC. In this study, we report that an epigenetically altered mesenchymal stem cell niche, termed high-risk mesenchymal stromal/stem cell (hrMSC), exists prior to STIC lesion formation. hrMSCs are enriched in STIC stroma and contribute to a stromal \"field effect\" extending beyond the borders of the STIC lesion. hrMSCs promote DNA damage in FTE cells while also fostering FTE cell survival. hrMSCs induce malignant transformation of the FTE, resulting in metastatic cancer in vivo, indicating that hrMSCs promote cancer initiation. hrMSCs are significantly enriched in BRCA1/2 mutation carriers and increase with age. Combined, these findings indicate that hrMSCs can incite ovarian cancer initiation and have important implications for ovarian cancer detection and prevention.</p><p><strong>Significance: </strong>This work demonstrates a critical role of fallopian tube stromal cells in HGSOC initiation with implications for the pathophysiology of HGSOC formation and the development of prevention and early detection strategies critically needed in this disease. Additionally, the identification of stromal-mediated epithelial transformation has broad implications for understanding pan-cancer initiation. See related commentary by Recouvreux and Orsulic, p. 1093.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"1203-1224"},"PeriodicalIF":29.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623621","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":"Antitumor Activity of Vebreltinib and Characterization of Clinicogenomic Features in Solid Tumors with MET Rearrangements.","authors":"Seshiru Nakazawa, Federica Pecci, Igor Odintsov, Dimitris Gazgalis, Felix H Gottlieb, Biagio Ricciuti, Lodovica Zullo, Joao V Alessi, Alessandro Di Federico, Mihaela Aldea, Edoardo Garbo, Malini M Gandhi, Arushi Saini, William W Feng, Jie Jiang, Simon Baldacci, Francesco Facchinetti, Maisam Makarem, Marie-Anaïs Locquet, Koji Haratani, Danielle Haradon, Benjamin Besse, Antoine Italiano, Jordi Remon, Pernelle Lavaud, Damien Vasseur, David Planchard, Yusuke Sato, Yukako Watanabe, Scott Owen, Alexis B Cortot, Hoda Mahran, Martin D Forster, Jiaxin Niu, Pascale Tomasini, Swan Swan Leong, Kevin Tay, Emilio Esteban, Anna Minchom, Sani H Kizilbash, Marcia Cruz-Correa, Kin-Hung Peony Yu, Xiaoling Zhang, Pan Chen, Mythili Sangem, Jianwei Che, Lynette M Sholl, Pasi A Jänne, Mark M Awad","doi":"10.1158/2159-8290.CD-24-1726","DOIUrl":"10.1158/2159-8290.CD-24-1726","url":null,"abstract":"<p><p>Oncogenic translocations involving the MET gene have been reported in several cancer types, but detailed clinicogenomic characterization of these cancers is not well defined. In addition, prospective clinical trials evaluating the antitumor activity of MET inhibitors in MET rearrangement-positive cancers are limited. In this study, in a pan-cancer analysis of >46,000 solid tumors with comprehensive genomic profiling, we identified oncogenic MET rearrangements in ∼0.04% of cancers. Preliminary analysis from a phase II clinical trial of the type I MET tyrosine kinase inhibitor (TKI) vebreltinib in MET fusion-positive solid tumors demonstrated an objective response rate of 50% and disease control rate of 79%, with antitumor activity seen in diverse cancer types, including lung adenocarcinoma and intrahepatic cholangiocarcinoma, among others. Similar to MET exon 14-altered lung cancer, secondary mutations in the kinase domain can confer resistance to MET TKIs in MET fusion-positive cancers. Overall, these data categorize MET rearrangements as actionable targets in solid tumors.</p><p><strong>Significance: </strong>MET rearrangement-positive cancers are not well-characterized, and optimal treatment strategies are yet to be defined. Through comprehensive genomic analysis, preclinical modeling, and preliminary results of a phase II clinical trial, we demonstrate that MET fusions are a unique molecular subtype of cancers targetable with vebreltinib, a TKI in development.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"1129-1140"},"PeriodicalIF":29.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810522","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":"Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma.","authors":"Tanjina Kader, Jia-Ren Lin, Clemens B Hug, Shannon Coy, Yu-An Chen, Ino de Bruijn, Natalie Shih, Euihye Jung, Roxanne J Pelletier, Mariana Lopez Leon, Gabriel Mingo, Dalia K Omran, Jong Suk Lee, Clarence Yapp, Baby A Satravada, Ritika Kundra, Yilin Xu, Sabrina Chan, Juliann B Tefft, Jeremy L Muhlich, Sarah H Kim, Stefan M Gysler, Judith Agudo, James R Heath, Nikolaus Schultz, Charles W Drescher, Peter K Sorger, Ronny Drapkin, Sandro Santagata","doi":"10.1158/2159-8290.CD-24-1366","DOIUrl":"10.1158/2159-8290.CD-24-1366","url":null,"abstract":"<p><p>High-grade serous ovarian cancer (HGSOC) originates from fallopian tube (FT) precursors. However, the molecular changes that occur as precancerous lesions progress to HGSOC are not well understood. To address this, we integrated high-plex imaging and spatial transcriptomics to analyze human tissue samples at different stages of HGSOC development, including p53 signatures, serous tubal intraepithelial carcinomas (STIC), and invasive HGSOC. Our findings reveal immune modulating mechanisms within precursor epithelium, characterized by chromosomal instability, persistent IFN signaling, and dysregulated innate and adaptive immunity. FT precursors display elevated expression of MHC class I, including HLA-E, and IFN-stimulated genes, typically linked to later-stage tumorigenesis. These molecular alterations coincide with progressive shifts in the tumor microenvironment, transitioning from immune surveillance in early STICs to immune suppression in advanced STICs and cancer. These insights identify potential biomarkers and therapeutic targets for HGSOC interception and clarify the molecular transitions from precancer to cancer.</p><p><strong>Significance: </strong>This study maps the immune response in FT precursors of HGSOC, highlighting localized IFN signaling, chromosomal instability, and competing immune surveillance and suppression along the progression axis. It provides an explorable public spatial profiling atlas for investigating precancer mechanisms, biomarkers, and early detection and interception strategies. See related commentary by Recouvreux and Orsulic, p. 1093.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"1180-1202"},"PeriodicalIF":29.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863423","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":"Editor's Note: Small-Molecule Inhibition of the Acyl-Lysine Reader ENL as a Strategy against Acute Myeloid Leukemia.","authors":"Yiman Liu, Qinglan Li, Fatemeh Alikarami, Declan R Barrett, Leila Mahdavi, Hangpeng Li, Sylvia Tang, Tanweer A Khan, Mayako Michino, Connor Hill, Lele Song, Lu Yang, Yuanyuan Li, Sheela Pangeni Pokharel, Andrew W Stamford, Nigel Liverton, Louis M Renzetti, Simon Taylor, Gillian F Watt, Tammy Ladduwahetty, Stacia Kargman, Peter T Meinke, Michael A Foley, Junwei Shi, Haitao Li, Martin Carroll, Chun-Wei Chen, Alessandro Gardini, Ivan Maillard, David J Huggins, Kathrin M Bernt, Liling Wan","doi":"10.1158/2159-8290.CD-25-0674","DOIUrl":"10.1158/2159-8290.CD-25-0674","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"15 6","pages":"1297-1298"},"PeriodicalIF":29.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207811","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":"Before They Were Malignant.","authors":"Maria Sol Recouvreux, Sandra Orsulic","doi":"10.1158/2159-8290.CD-25-0429","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-25-0429","url":null,"abstract":"<p><p>A lack of understanding of how ovarian cancer originates in fallopian tube cells has hindered early detection and prevention, often resulting in diagnosis at advanced stages when treatment options are limited. In this issue of Cancer Discovery, two studies uncover critical microenvironmental changes that drive tumor initiation and progression, offering potential targets for earlier intervention. See related article by Kader et al., p. 1180 See related article by Garcia et al., p. 1203.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"15 6","pages":"1093-1095"},"PeriodicalIF":29.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207809","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}