Targeting DNA Damage Response Pathways in Cancer

Abdulrahman, GO; Curtin, NJ

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

Targeting DNA Damage Response Pathways in Cancer

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

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

Abstract

© 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.