1. BRCA, HRR Deficiency, and PARP Inhibitors

2. Outline

3. Cancer Suppression by BRCA1 and BRCA2

4. DNA Repair Pathways

5. DDR: Molecular Mechanisms

6. DDR as a Target in Cancer

7. Mechanism of Action: PARP Inhibitors (Olaparib, Rucaparib, Niraparib, Talazoparib, Veliparib)

8. Hereditary Cancer

9. Effect of PARP Inhibitors on BRCA1/2 Mutated Cells

10. Synthetic Lethality: Preclinical Data

11. Synthetic Lethality Targeting in BRCA1 or BRCA2 Mutations: Proof-of-Concept Trials with Olaparib

12. "BRCAness" Syndrome in Ovarian Cancer: A Case-Control Study

13. Why Prescribe a PARP Inhibitor After Response to Platinum-Based Chemotherapy?

14. Platinum-Based Chemotherapy Followed by PARP Inhibitor in Advanced Ovarian Cancer: Phase 3 Study Design

15. Niraparib in Advanced Ovarian Cancer: NOVA Trial

16. Olaparib in Advanced Ovarian Cancer: SOLO2 Trial

17. Rucaparib in Advanced Ovarian Cancer: ARIEL3 Trial

18. Platinum-Based Chemotherapy Followed by PARP Inhibitor in Advanced Ovarian Cancer: PFS and Other Parameters

19. PARP Inhibitors in Monotherapy in Advanced Ovarian Cancer: Study 10 and ARIEL2 (Rucaparib)

20. PARP Inhibitors in Monotherapy: ORR in the Efficacy Population

21. Phase 2 Study of Olaparib in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation (Study 42)

22. Study 42: Pancreatic Cancer Subgroup

23. POLO-1 Design

24. RUCAPANC Study: Phase 2 of Rucaparib in Patients With Pancreatic Cancer and a Germline or Somatic BRCA Mutation

25. RUCAPANC Investigator-Assessed Confirmed Responses by RECIST

26. OlympiAD Phase 3 Trial: Olaparib for MBC in Patients With a Germline BRCA Mutation

27. EMBRACA: Talazoparib in Advanced gBRCA Breast Cancer

28. OlympiA: Phase 3 Study of Olaparib vs Placebo as Adjuvant Treatment in gBRCA and High-Risk HER2-Negative Primary Breast Cancer

29. Germline Aberrations in DNA Repair in mCRPC

30. Conclusions

31. Conclusions (cont)

32. Abbreviations

33. Abbreviations (cont)

34. Abbreviations (cont)

35. Abbreviations (cont)