2021
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 cancers
2019
Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51
Kaplan AR, Gueble SE, Liu Y, Oeck S, Kim H, Yun Z, Glazer PM. Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51. Science Translational Medicine 2019, 11 PMID: 31092693, PMCID: PMC6626544, DOI: 10.1126/scitranslmed.aav4508.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBRCA1 ProteinBRCA2 ProteinCell Line, TumorDNA RepairDown-RegulationE2F4 Transcription FactorFemaleGene Expression Regulation, NeoplasticHumansMice, NudePoly(ADP-ribose) Polymerase InhibitorsQuinazolinesRad51 RecombinaseReceptors, Platelet-Derived Growth FactorTumor HypoxiaVascular Endothelial Growth Factor Receptor-2Xenograft Model Antitumor AssaysConceptsHomology-directed DNA repairDNA repairE2F transcription factor 4Protein phosphatase 2ATranscription factor 4DNA repair inhibitorsPhosphatase 2ARAD51 recombinaseTranscriptional corepressorMouse tumor xenograftsSynthetic lethalityGene expressionRB2/Mouse bone marrowGrowth factor receptor inhibitionRepair inhibitorsUnknown mechanismPlatelet-derived growth factor receptor inhibitionFactor 4Human tumorsInhibitor olaparibPARP inhibitorsMutationsCombination of cediranibCancer therapy