{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["52"],"submitter":["Roggero CM"],"pubmed_abstract":["Despite widespread deregulation of CDK4/6 activity in non-small cell lung cancer (NSCLC), clinical trials with CDK4/6 inhibitor (CDK4/6i) as a monotherapy have shown poor antitumor activity. Preclinical studies indicate that CDK4/6i may collaborate by influencing DNA damage repair pathways during radiotherapy. Since PARP1 expression was also significantly upregulated in NSCLC, we analyzed the efficacy of combining PARP1 and CDK4/6 inhibition in NSCLC models. We found that CDK4/6is synergize with PARP1 inhibitors (PARPis) to inhibit the clonogenic growth of RB-proficient NSCLC models. This synergy correlates with increased accumulation of DNA damage, interrupted cell-cycle checkpoints, and enhanced apoptotic cell death. Mechanistically, we showed that CDK4/6is promote PARP1 protein degradat"],"journal":["Translational oncology"],"pagination":["102231"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11683282"],"repository":["biostudies-literature"],"pubmed_title":["CDK4/6 inhibitors promote PARP1 degradation and synergize with PARP inhibitors in non-small cell lung cancer."],"pmcid":["PMC11683282"],"pubmed_authors":["Raj GV","Yin Y","Ma S","Roggero CM","Devineni A","Ghosh AB","Blatt E"],"additional_accession":[]},"is_claimable":false,"name":"CDK4/6 inhibitors promote PARP1 degradation and synergize with PARP inhibitors in non-small cell lung cancer.","description":"Despite widespread deregulation of CDK4/6 activity in non-small cell lung cancer (NSCLC), clinical trials with CDK4/6 inhibitor (CDK4/6i) as a monotherapy have shown poor antitumor activity. Preclinical studies indicate that CDK4/6i may collaborate by influencing DNA damage repair pathways during radiotherapy. Since PARP1 expression was also significantly upregulated in NSCLC, we analyzed the efficacy of combining PARP1 and CDK4/6 inhibition in NSCLC models. We found that CDK4/6is synergize with PARP1 inhibitors (PARPis) to inhibit the clonogenic growth of RB-proficient NSCLC models. This synergy correlates with increased accumulation of DNA damage, interrupted cell-cycle checkpoints, and enhanced apoptotic cell death. Mechanistically, we showed that CDK4/6is promote PARP1 protein degradat","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2025-04-04T08:11:47.662Z","creation":"2025-04-04T08:11:47.662Z"},"accession":"S-EPMC11683282","cross_references":{"pubmed":["39662449"],"doi":["10.1016/j.tranon.2024.102231"]}}