Lookup NU author(s): Dr Ganiy Abdulrahman,
Professor Nicola Curtin
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© 2017 Elsevier Ltd. All rights reserved. The DNA damage response (DDR), comprising DNA repair and cell-cycle checkpoint pathways, is an attractive target for cancer therapy. DDR inhibitors have been developed to (i) overcome DDR-mediated resistance to DNA-damaging anticancer therapy and (ii) exploit DDR dysfunction in cancer by targeting complementary pathways. The latter approach, exemplified by poly(ADP-ribose) polymerase (PARP) inhibitors in tumors with BRCA1 or BRCA2 mutations, is predicted to be more tumor-selective.This review describes the role of PARP and DNA-dependent protein kinase in DNA repair and ataxia-telangiectasia-mutated/checkpoint kinase 2 and ATM and Rad3-related/checkpoint kinase 1 in cell-cycle checkpoints, the preclinical development of inhibitors of these key proteins, published clinical trial data, and the current trials.
Author(s): Abdulrahman GO, Curtin NJ
Editor(s): Samuel Chackalamannil, David Rotella and Simon Ward
Publication type: Book Chapter
Publication status: Published
Book Title: Comprehensive Medicinal Chemistry III
Online publication date: 13/06/2017
Acceptance date: 02/04/2016
Publisher: Elsevier Inc.
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