Poly (ADP-ribose) polymerase inhibitors
Ratner ES, Sartorelli AC, Lin ZP. Poly (ADP-ribose) polymerase inhibitors. Current Opinion In Oncology 2012, 24: 564-571. PMID: 22759740, PMCID: PMC3799945, DOI: 10.1097/cco.0b013e3283564230.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerOvarian cancerOverall survivalEOC patientsPARP inhibitorsBRCA mutationsHereditary epithelial ovarian cancerLower chemotherapy response rateDNA repair defectsDeleterious BRCA1/2 mutationsPlatinum-based chemotherapyRecurrence-free survivalChemotherapy response rateRecent clinical trialsPoor overall survivalNew treatment optionsShorter survival timeSporadic epithelial ovarian cancerPoly (ADP-ribose) polymerasePoly (ADP-ribose) polymerase (PARP) inhibitorsEffect of cisplatinPARP inhibitor olaparibRecurrent diseaseClinical outcomesTherapeutic challengeIn silico screening identifies a novel small molecule inhibitor that counteracts PARP inhibitor resistance in ovarian cancer
Lin ZP, Al Zouabi NN, Xu ML, Bowen NE, Wu TL, Lavi ES, Huang PH, Zhu YL, Kim B, Ratner ES. In silico screening identifies a novel small molecule inhibitor that counteracts PARP inhibitor resistance in ovarian cancer. Scientific Reports 2021, 11: 8042. PMID: 33850183, PMCID: PMC8044145, DOI: 10.1038/s41598-021-87325-5.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerSmall molecule inhibitorsPARP inhibitor resistancePARP inhibitorsBRCA mutationsOvarian cancerEOC cellsPoly ADP-ribose polymerase inhibitorsMolecule inhibitorsInhibitor resistanceADP-ribose polymerase inhibitorsTumor-bearing miceNovel small molecule inhibitorPARP inhibitor olaparibDefective homologous recombination (HR) repairEOC xenograftsClinical efficacySurvival timePutative small molecule inhibitorsInhibitor olaparibPolymerase inhibitorsHR repairInhibitorsCancerHomologous recombination repairCombination of triapine, olaparib, and cediranib suppresses progression of BRCA-wild type and PARP inhibitor-resistant epithelial ovarian cancer
Lin ZP, Zhu YL, Lo YC, Moscarelli J, Xiong A, Korayem Y, Huang PH, Giri S, LoRusso P, Ratner ES. Combination of triapine, olaparib, and cediranib suppresses progression of BRCA-wild type and PARP inhibitor-resistant epithelial ovarian cancer. PLOS ONE 2018, 13: e0207399. PMID: 30444904, PMCID: PMC6239325, DOI: 10.1371/journal.pone.0207399.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBRCA1 ProteinBreast NeoplasmsCell Line, TumorDrug Resistance, NeoplasmFemaleHumansMice, NudeMice, SCIDPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsPyridinesQuinazolinesThiosemicarbazonesXenograft Model Antitumor AssaysConceptsEpithelial ovarian cancerBRCA wild typeSCID-beige miceXenograft mouse modelOvarian cancerMouse modelSurvival timeNude micePARP inhibitorsEOC cell linesPARP inhibitor olaparibHomologous recombination repairCombination regimentsDefective homologous recombination (HR) repairEOC growthC tumorsSignificant prolongationBRCA mutationsAbdominal circumferenceEOC cellsSingle drugCediranibMarked suppressionTriple combinationTumor growth