Successes and Challenges of PARP Inhibitors in Cancer Therapy.

Tiffany K Ricks,Gwynn Ison,Haw-Jyh Chiu,Richard Pazdur,Geoffrey Kim,Amy E Mckee,Paul Kluetz

doi:10.3389/fonc.2015.00222

Abstract

Successes and Challenges of PARP Inhibitors in Cancer Therapy.

Highlights

Successes and challenges of Poly (ADP-ribose) polymerases (PARPs) inhibitors in cancer therapyTiffany K. Ricks*, Haw-Jyh Chiu, Gwynn Ison, Geoffrey Kim, Amy E. McKee, Paul Kluetz and Richard Pazdur Office of Hematology and Oncology Products (OHOP), Office of New Drugs (OND), Center for Drug Evaluation and Research (CDER), U.S Food and Drug Administration, Silver Spring, MD, USA Keywords: PARP inhibitor, cancer, drug resistance, BRCA1, BRCA2, homologous recombination Specialty section: This article was submitted to Cancer Molecular Targets and Therapeutics, a section of the journal Frontiers in Oncology Citation: Ricks TK, Chiu H-J, Ison G, Kim G, McKee AE, Kluetz P and Pazdur R (2015) Successes and challenges of PARP inhibitors in cancer therapy. Front. Oncol. 5:222
(ADP-ribose) polymerases (PARPs) are a family of enzymes involved in cellular homeostasis, including DNA transcription, cell-cycle regulation, and DNA repair [1, 2]
In the absence of Poly (ADP-ribose) polymerases (PARPs) activity, unrepaired SSBs can lead to more deleterious double strand breaks (DSBs), which require high fidelity, homologous recombination (HR) or low fidelity, non-homologous end joining (NHEJ) for repair

Summary

Successes and challenges of PARP inhibitors in cancer therapy

Tiffany K. Ricks*, Haw-Jyh Chiu, Gwynn Ison, Geoffrey Kim, Amy E. McKee, Paul Kluetz and Richard Pazdur Office of Hematology and Oncology Products (OHOP), Office of New Drugs (OND), Center for Drug Evaluation and Research (CDER), U.S Food and Drug Administration, Silver Spring, MD, USA Keywords: PARP inhibitor, cancer, drug resistance, BRCA1, BRCA2, homologous recombination Specialty section: This article was submitted to Cancer Molecular Targets and Therapeutics, a section of the journal Frontiers in Oncology Citation: Ricks TK, Chiu H-J, Ison G, Kim G, McKee AE, Kluetz P and Pazdur R (2015) Successes and challenges of PARP inhibitors in cancer therapy. Front. Oncol. 5:222.

INTRODUCTION

Monotherapy Monotherapy

Ovarian Breast Ovarian

FUTURE CHALLENGES OF PARP INHIBITOR DEVELOPMENT

Findings

CONCLUSION