{"doi":"10.21873/anticanres.16754","title":"PARP Inhibitor Sensitizes<i>BRCA</i>-mutant Pancreatic Cancer to Oxaliplatin by Suppressing the CDK1/BRCA1 Axis","abstract":null,"journal":"Anticancer Research","year":2023,"id":635696,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1649365,"name":"DANBEE KIM","orcid":null,"position":1,"is_corresponding":false},{"id":1649366,"name":"DA SOL LEE","orcid":null,"position":2,"is_corresponding":false},{"id":1649367,"name":"SEONMIN LEE","orcid":null,"position":3,"is_corresponding":false},{"id":1649369,"name":"CHANGHOON YOO","orcid":null,"position":4,"is_corresponding":false},{"id":1649370,"name":"KYU-PYO KIM","orcid":null,"position":5,"is_corresponding":false},{"id":1649364,"name":"CHORONG KIM","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"PARP Inhibitor Sensitizes<i>BRCA</i>-mutant Pancreatic Cancer to Oxaliplatin by Suppressing the CDK1/BRCA1 Axis","abstract":"BACKGROUND/AIM: Currently, olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has been approved as maintenance therapy for patients with germline BRCA mutations and metastatic pancreatic cancer. However, platinum-based chemotherapy, which induces synthetic lethality with PARP inhibitor treatment, is still controversial. Hence, we aimed to examine a platinum-based drug in combination with a PARP inhibitor and generate data regarding the use of a PARP inhibitor in the overall treatment of pancreatic cancer. MATERIALS AND METHODS: Using the Capan-1 cell line (BRCA2-mutant pancreatic cancer cell line), we evaluated the combinatorial effects of olaparib, a PARP inhibitor, and oxaliplatin by cell viability, combination index, western blotting, immunocytochemistry, flow cytometry, apoptosis assays and in vivo experiments. RESULTS: Capan-1 cells showed high sensitivity to olaparib due to the alteration in PARP activity, which led to cell death through the accumulation of oxaliplatin-induced DNA damage. Beyond DNA damage, oxaliplatin also suppressed the CDK1/BRCA1 signaling axis, which induced defects in homologous recombination repair. Additionally, inhibition of CDK1, a biomarker for oxaliplatin efficacy, induced cell death regardless of the BRCA mutation profile. CONCLUSION: Oxaliplatin may be used in combination with olaparib in PDAC patients with DNA damage repair mutations. Our findings highlight CDK1 as a potential therapeutic target for pancreatic cancer.","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38030179","pmcid":null,"openalex_id":"https://openalex.org/W4389134950","authors":[],"funders":[],"total_grants":0,"fwci":0.231,"citation_percentile":0.54356204,"influential_citations":0,"citation_trend":[{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://syndication.highwire.org/content/doi/10.21873/anticanres.16754","host_type":"publisher"},{"url":"https://doi.org/10.21873/anticanres.16754","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38030179","host_type":"repository"}],"fields_of_study":["PARP inhibition in cancer therapy","Advanced Breast Cancer Therapies","Cancer-related Molecular Pathways"],"mesh_terms":["Poly(ADP-ribose) Polymerase Inhibitors","Oxaliplatin","DNA Damage","DNA Repair","Humans","Pancreatic Neoplasms","Phthalazines","Poly(ADP-ribose) Polymerases","CDC2 Protein Kinase","BRCA1 Protein"],"keywords":["Olaparib","PARP inhibitor","Veliparib","Cancer research","Oxaliplatin","Pancreatic cancer","Synthetic lethality","Poly ADP ribose polymerase","DNA repair","Cancer","Biology","Medicine","Internal medicine","Polymerase","Colorectal cancer","Genetics","DNA","BRCA2"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T15:27:26.975858Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}