{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Durinikova E"],"funding":["Ministero Salute","CRUK Advanced Clinician Scientist Award","Cancer Research UK","European Union&apos;s Horizon 2020","CRUK Early Detection Project award","AIRC","National Institute for Health Research (NIHR)","Fondazione AIRC","AIRC IG","FC AECC","Cambridge Biomedical Research Centre"],"pagination":["3874-3889"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9433963"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["28(17)"],"pubmed_abstract":["<h4>Purpose</h4>Genomic instability is a hallmark of cancer and targeting DNA damage response (DDR) is emerging as a promising therapeutic strategy in different solid tumors. The effectiveness of targeting DDR in colorectal cancer has not been extensively explored.<h4>Experimental design</h4>We challenged 112 cell models recapitulating the genomic landscape of metastatic colorectal cancer with ATM, ATR, CHK1, WEE1, and DNA-PK inhibitors, in parallel with chemotherapeutic agents. We focused then on ATR inhibitors (ATRi) and, to identify putative biomarkers of response and resistance, we analyzed at multiple levels colorectal cancer models highly sensitive or resistant to these drugs.<h4>Results</h4>We found that around 30% of colorectal cancers, including those carrying KRAS and BRAF mutati"],"journal":["Clinical cancer research : an official journal of the American Association for Cancer Research"],"pubmed_title":["Targeting the DNA Damage Response Pathways and Replication Stress in Colorectal Cancer."],"pmcid":["PMC9433963"],"funding_grant_id":["22932","20236","20685","23916","A28223","22795","2020","23433","21923","GEACC18004TAB","27815","2018-ID","C60100","A26825","A27815","BRC-125-20014","NIHR301607","CP 12/2018 IANG CRC","25274","101020342","C60100/A27815","IS-BRC-1215-20014","C60100/A23916","A23916"],"pubmed_authors":["Siena S","Durinikova E","Degasperi A","Bardelli A","Lamba S","Sartore-Bianchi A","Dias JML","Grasso G","Corti G","Lorenzato A","Nik-Zainal S","Marsoni S","Cancelliere C","Mauri G","Pisati F","Chila R","Linnebacher M","Reilly NM","Buzo K","Arena S","Mariella E","Andrei P","Di Nicolantonio F"],"additional_accession":[]},"is_claimable":false,"name":"Targeting the DNA Damage Response Pathways and Replication Stress in Colorectal Cancer.","description":"<h4>Purpose</h4>Genomic instability is a hallmark of cancer and targeting DNA damage response (DDR) is emerging as a promising therapeutic strategy in different solid tumors. The effectiveness of targeting DDR in colorectal cancer has not been extensively explored.<h4>Experimental design</h4>We challenged 112 cell models recapitulating the genomic landscape of metastatic colorectal cancer with ATM, ATR, CHK1, WEE1, and DNA-PK inhibitors, in parallel with chemotherapeutic agents. We focused then on ATR inhibitors (ATRi) and, to identify putative biomarkers of response and resistance, we analyzed at multiple levels colorectal cancer models highly sensitive or resistant to these drugs.<h4>Results</h4>We found that around 30% of colorectal cancers, including those carrying KRAS and BRAF mutati","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2025-04-19T13:23:09.577Z","creation":"2025-04-19T13:23:09.577Z"},"accession":"S-EPMC9433963","cross_references":{"pubmed":["35881546"],"doi":["10.1158/1078-0432.CCR-22-0875"]}}