{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pilie PG"],"funding":["Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy","Cancer Prevention and Research Institute of Texas (CPRIT)","Conquer Cancer Foundation (CCF)","U.S. Department of Defense (DOD)","V Foundation for Cancer Research (VFCR)","Cancer Prevention and Research Institute of Texas","National Cancer Institute (NCI)","Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy (Khalifa Institute)","U.S. Department of Defense","National Cancer Institute","NCI NIH HHS","Conquer Cancer Foundation","V Foundation for Cancer Research"],"pagination":["2121-2139"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11094420"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["30(10)"],"pubmed_abstract":["<h4>Purpose</h4>Mutations in the ATM gene are common in multiple cancers, but clinical studies of therapies targeting ATM-aberrant cancers have yielded mixed results. Refinement of ATM loss of function (LOF) as a predictive biomarker of response is urgently needed.<h4>Experimental design</h4>We present the first disclosure and preclinical development of a novel, selective ATR inhibitor, ART0380, and test its antitumor activity in multiple preclinical cancer models. To refine ATM LOF as a predictive biomarker, we performed a comprehensive pan-cancer analysis of ATM variants in patient tumors and then assessed the ATM variant-to-protein relationship. Finally, we assessed a novel ATM LOF biomarker approach in retrospective clinical data sets of patients treated with platinum-based chemotherap"],"journal":["Clinical cancer research : an official journal of the American Association for Cancer Research"],"pubmed_title":["Ataxia-Telangiectasia Mutated Loss-of-Function Displays Variant and Tissue-Specific Differences across Tumor Types."],"pmcid":["PMC11094420"],"funding_grant_id":["P30 CA016672","RP150535","R01 CA255074","VC2020-001","R01-CA255074","OC200482"],"pubmed_authors":["Kyewalabye K","Armstrong L","Boursier M","Geo L","Johnson MG","Smith GCM","Kopetz SE","Giuliani V","Shaw KR","Goswamy RV","Meric-Bernstam F","Le H","Vellano CP","Yang D","Yap TA","Elinati E","Feng N","Grinkevich V","Liu CY","Jones P","Machado AA","Carroll CL","Wani KM","Geck Do MK","Lazar AJ","Likhatcheva M","Tse WY","Ma X","Bristow CA","Ngoi NYL","Sanchez NS","Majithiya J","Piscitello D","Marszalek JR","Gheeya JS","Di Francesco ME","Holla V","Luzarraga MR","Robinson HMR","McGrail DJ","Pilie PG","Rajendra E","Bardenhagen JP","Lively S","Ranzani M","Lillo G","Wang WL","Campbell E","Johnson TI","Heffernan TP","Neves J"],"additional_accession":[]},"is_claimable":false,"name":"Ataxia-Telangiectasia Mutated Loss-of-Function Displays Variant and Tissue-Specific Differences across Tumor Types.","description":"<h4>Purpose</h4>Mutations in the ATM gene are common in multiple cancers, but clinical studies of therapies targeting ATM-aberrant cancers have yielded mixed results. Refinement of ATM loss of function (LOF) as a predictive biomarker of response is urgently needed.<h4>Experimental design</h4>We present the first disclosure and preclinical development of a novel, selective ATR inhibitor, ART0380, and test its antitumor activity in multiple preclinical cancer models. To refine ATM LOF as a predictive biomarker, we performed a comprehensive pan-cancer analysis of ATM variants in patient tumors and then assessed the ATM variant-to-protein relationship. Finally, we assessed a novel ATM LOF biomarker approach in retrospective clinical data sets of patients treated with platinum-based chemotherap","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-02T08:17:53.994Z","creation":"2026-05-26T03:07:25.553Z"},"accession":"S-EPMC11094420","cross_references":{"pubmed":["38416404"],"doi":["10.1158/1078-0432.CCR-23-1763"]}}