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An Introduction to DNA Damage Repair in Cancer: Beyond PARP

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Presentation on theme: "An Introduction to DNA Damage Repair in Cancer: Beyond PARP"— Presentation transcript:

1 An Introduction to DNA Damage Repair in Cancer: Beyond PARP

2 Program Goals

3 Discussion Overview

4 DNA Repair

5 ABCs of DNA Repair

6 DNA Repair Defects in Cancer

7 DNA Repair Defects: The Achilles’ Heel in Cancer Cells

8 Synthetic Lethality

9 PARP and Synthetic Lethality

10 Increased Sensitivity of BRCA1-/- and BRCA2-/- Cells to PARP Inhibition

11 PARP Inhibitors

12 "BRCAness"

13 Sensitivity to PARP Inhibition in Cells Deficient for DNA Repair

14 What Have We Learned From Clinical Trials of PARP Inhibitors?

15 Inhibition of PARP in Tumors From Carriers of BRCA Mutations

16 Platinum-Free Interval Relative to Olaparib Sensitivity

17 Platinum Sensitivity in BRCA1-/- Ovarian Cancer Patient After PD on Olaparib

18 Class Effect of PARP Inhibitors

19 Olaparib Induces Responses in mCRPC

20 PARP Inhibition in Patients Heterozygous for ATM

21 Targeting DNA Repair Beyond PARP

22 Targeting DNA Repair Through ATR

23 ATR Inhibitor VX-970

24 VX-970 Monotherapy Complete Response

25 Combination Therapies Potentially Synergistic With DNA Repair

26 Other Targetable DNA Repair Defects

27 Conclusions

28 Abbreviations

29 Abbreviations (cont)

30 Abbreviations (cont)

31 Abbreviations (cont)


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