{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Segeren HA"],"funding":["Dutch Research Council (NWO)","ZonMw"],"pagination":["2719-2733"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9076537"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["41(19)"],"pubmed_abstract":["Cancer cells often experience high basal levels of DNA replication stress (RS), for example due to hyperactivation of oncoproteins like MYC or RAS. Therefore, cancer cells are considered to be sensitive to drugs that exacerbate the level of RS or block the intra S-phase checkpoint. Consequently, RS-inducing drugs including ATR and CHK1 inhibitors are used or evaluated as anti-cancer therapies. However, drug resistance and lack of biomarkers predicting therapeutic efficacy limit efficient use. This raises the question what determines sensitivity of individual cancer cells to RS. Here, we report that oncogenic RAS does not only enhance the sensitivity to ATR/CHK1 inhibitors by directly causing RS. Instead, we observed that HRAS<sup>G12V</sup> dampens the activation of the P53-dependent trans"],"journal":["Oncogene"],"pubmed_title":["Oncogenic RAS sensitizes cells to drug-induced replication stress via transcriptional silencing of P53."],"pmcid":["PMC9076537"],"funding_grant_id":["184.034.019","91116011"],"pubmed_authors":["van Liere EA","Segeren HA","de Bruin A","Westendorp B","Riemers FM"],"additional_accession":[]},"is_claimable":false,"name":"Oncogenic RAS sensitizes cells to drug-induced replication stress via transcriptional silencing of P53.","description":"Cancer cells often experience high basal levels of DNA replication stress (RS), for example due to hyperactivation of oncoproteins like MYC or RAS. Therefore, cancer cells are considered to be sensitive to drugs that exacerbate the level of RS or block the intra S-phase checkpoint. Consequently, RS-inducing drugs including ATR and CHK1 inhibitors are used or evaluated as anti-cancer therapies. However, drug resistance and lack of biomarkers predicting therapeutic efficacy limit efficient use. This raises the question what determines sensitivity of individual cancer cells to RS. Here, we report that oncogenic RAS does not only enhance the sensitivity to ATR/CHK1 inhibitors by directly causing RS. Instead, we observed that HRAS<sup>G12V</sup> dampens the activation of the P53-dependent trans","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2026-05-31T21:57:40.915Z","creation":"2025-04-04T19:30:24.86Z"},"accession":"S-EPMC9076537","cross_references":{"pubmed":["35393546"],"doi":["10.1038/s41388-022-02291-0"]}}