IMR Press / FBL / Volume 18 / Issue 4 / DOI: 10.2741/4188

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Review

Poly(ADP-ribose) polymerase inhibitors as cancer therapy

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1 Early Drug Development Center, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA
Academic Editor:Adriana De Siervi
Front. Biosci. (Landmark Ed) 2013, 18(4), 1392–1406; https://doi.org/10.2741/4188
Published: 1 June 2013
(This article belongs to the Special Issue BRCA1 and BRCA2 role in cancer)
Abstract

Poly(ADP-ribose) polymerase (PARP) inhibitors are pharmacologic agents which primarily inhibit the PARP-1 and PARP-2 enzymes within the cell. Inhibition of PARP results in failure of base-excision repair (BER) to correct single-stranded breaks in DNA. This failure results in double-stranded breaks that are subsequently repaired either by homologous recombination (HR) repair, which is error-free, or by non-homologous end joining (NHEJ), which is an errorprone process. Clinically, PARP inhibitors demonstrate activity in tumors which lack a functional HR system (i.e. BRCA1 and BRCA2 mutations) by forcing NHEJ repair. Known as synthetic lethality, the use of NHEJ in these tumors generates genomic instability and eventual cell death due to rapid development of non-viable genetic errors. In addition due their BER effects, PARP inhibitors are being developed as chemotherapy and radiation sensitizers in a number of tumor types. This review will examine the role of the PARP enzymes in DNA repair, PARP inhibitors in HR-deficient tumors, current results of clinical studies of PARP inhibitors and research efforts to expand the clinical activity of PARP inhibitors beyond HR-deficient tumors.

Keywords
PARP inhibitors
BRCA1
BRCA2
breast cancer
ovarian cancer
homologous recombination
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