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BRCA, HRR Deficiency, and PARP Inhibitors
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Outline
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Cancer Suppression by BRCA1 and BRCA2
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DNA Repair Pathways
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DDR: Molecular Mechanisms
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DDR as a Target in Cancer
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Mechanism of Action: PARP Inhibitors (Olaparib, Rucaparib, Niraparib, Talazoparib, Veliparib)
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Hereditary Cancer
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Effect of PARP Inhibitors on BRCA1/2 Mutated Cells
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Synthetic Lethality: Preclinical Data
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Synthetic Lethality Targeting in BRCA1 or BRCA2 Mutations: Proof-of-Concept Trials with Olaparib
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"BRCAness" Syndrome in Ovarian Cancer: A Case-Control Study
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Why Prescribe a PARP Inhibitor After Response to Platinum-Based Chemotherapy?
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Platinum-Based Chemotherapy Followed by PARP Inhibitor in Advanced Ovarian Cancer: Phase 3 Study Design
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Niraparib in Advanced Ovarian Cancer: NOVA Trial
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Olaparib in Advanced Ovarian Cancer: SOLO2 Trial
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Rucaparib in Advanced Ovarian Cancer: ARIEL3 Trial
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Platinum-Based Chemotherapy Followed by PARP Inhibitor in Advanced Ovarian Cancer: PFS and Other Parameters
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PARP Inhibitors in Monotherapy in Advanced Ovarian Cancer: Study 10 and ARIEL2 (Rucaparib)
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PARP Inhibitors in Monotherapy: ORR in the Efficacy Population
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Phase 2 Study of Olaparib in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation (Study 42)
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Study 42: Pancreatic Cancer Subgroup
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POLO-1 Design
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RUCAPANC Study: Phase 2 of Rucaparib in Patients With Pancreatic Cancer and a Germline or Somatic BRCA Mutation
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RUCAPANC Investigator-Assessed Confirmed Responses by RECIST
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OlympiAD Phase 3 Trial: Olaparib for MBC in Patients With a Germline BRCA Mutation
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EMBRACA: Talazoparib in Advanced gBRCA Breast Cancer
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OlympiA: Phase 3 Study of Olaparib vs Placebo as Adjuvant Treatment in gBRCA and High-Risk HER2-Negative Primary Breast Cancer
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Germline Aberrations in DNA Repair in mCRPC
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Conclusions
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Conclusions (cont)
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Abbreviations
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Abbreviations (cont)
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Abbreviations (cont)
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Abbreviations (cont)
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