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DNA repair dysregulation from cancer driver to therapeutic target

Lookup NU author(s): Professor Nicola CurtinORCiD

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Abstract

Dysregulation of DNA damage repair and signalling to cell cycle checkpoints, known as the DNA damage response (DDR), is associated with a predisposition to cancer and affects responses to DNA-damaging anticancer therapy. Dysfunction of one DNA repair pathway may be compensated for by the function of another compensatory DDR pathway, which may be increased and contribute to resistance to DNA-damaging chemotherapy and radiotherapy. Therefore, DDR pathways make an ideal target for therapeutic intervention; first, to prevent or reverse therapy resistance; and second, using a synthetic lethal approach to specifically kill cancer cells that are dependent on a compensatory DNA repair pathway for survival in the context of cancer-associated oxidative and replicative stress. These hypotheses are currently being tested in the laboratory and are being translated into clinical studies

Publication metadata

Author(s): Curtin NJ

Publication type: Review

Publication status: Published

Journal: Nature Reviews Cancer

Year: 2012

Volume: 12

Issue: 12

Pages: 801-817

Print publication date: 01/12/2012

ISSN (print): 1474-175X

ISSN (electronic): 1474-1768

Publisher: NATURE PUBLISHING GROUP

URL: http://dx.doi.org/10.1038/nrc3399

DOI: 10.1038/nrc3399

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