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Targeting DNA Damage Response Pathways in Cancer

Lookup NU author(s): Dr Ganiy Abdulrahman, Professor Nicola CurtinORCiD


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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.

Publication metadata

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

Year: 2017

Volume: 5-8

Pages: 104-133

Online publication date: 13/06/2017

Acceptance date: 02/04/2016

Publisher: Elsevier Inc.


DOI: 10.1016/B978-0-12-409547-2.12394-7

Library holdings: Search Newcastle University Library for this item

ISBN: 9780128032015