BBIT20 inhibits homologous DNA repair with disruption of the BRCA1–BARD1 interaction in breast and ovarian cancer
Raimundo L, Paterna A, Calheiros J, Ribeiro J, Cardoso DSP, Piga I, Neto SJ, Hegan D, Glazer PM, Indraccolo S, Mulhovo S, Costa JL, Ferreira M, Saraiva L. BBIT20 inhibits homologous DNA repair with disruption of the BRCA1–BARD1 interaction in breast and ovarian cancer. British Journal Of Pharmacology 2021, 178: 3627-3647. PMID: 33899955, PMCID: PMC9124438, DOI: 10.1111/bph.15506.Peer-Reviewed Original ResearchConceptsTriple-negative breastOvarian cancerXenograft mouse modelMouse modelAntitumour activityAdvanced ovarian cancerCancer cellsPatient-derived cell linesHomologous DNA repairOvarian cancer cellsNon-malignant cellsPatient-derived cellsMarked synergistic effectAvailable therapiesCombination therapyCell cycle arrestReactive oxygen species generationSide effectsDNA repair-related genesSingle agentTherapeutic outcomesCancerOxygen species generationPersonalized treatmentResistant cancersClinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation
Kim J, Cardin DB, Vaishampayan UN, Kato S, Grossman SR, Glazer P, Shyr Y, Ivy SP, LoRusso P. Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. The Oncologist 2021, 26: e1104-e1109. PMID: 33742489, PMCID: PMC8265343, DOI: 10.1002/onco.13758.Peer-Reviewed Original ResearchConceptsMetastatic pancreatic adenocarcinomaHomologous recombination DNA repair deficiencyMetastatic pancreatic ductal adenocarcinomaPancreatic ductal adenocarcinomaOlaparib combinationStable diseaseBRCA mutationsAdverse eventsDuctal adenocarcinomaCommon treatment-related adverse eventsVascular endothelial growth factor receptor inhibitorEndothelial growth factor receptor inhibitorTreatment-related adverse eventsGrowth factor receptor inhibitorsPrior systemic chemotherapyMedian overall survivalObjective response rateGermline BRCA mutationsBest overall responseExpression of BRCA1/2Restaging scanCancer cell linesPrimary endpointStudy drugSystemic chemotherapy