Targeting DNA repair pathways: A novel approach to reduce cancer therapeutic resistance

Received 13 February 2009; received in revised form 16 June 2009; accepted 22 June 2009. published online 27 July 2009.

Summary

Increased chemo-resistance and radio-resistance of cancer cells is a major obstacle in the treatment and management of malignant cancers. An important mechanism that underlies the development of such therapeutic resistance is that cancer cells recognize DNA lesions induced by DNA-damaging agents and by ionizing radiation, and repair these lesions by activating various DNA repair pathways. Therefore, Use of pharmacological agents that can inhibit certain DNA repair pathways in cancer cells has the potential for enhancing the targeted cytotoxicity of anticancer treatments and reversing the associated therapeutic resistance associated with DNA repair; such agents, offering a promising opportunity to achieve better therapeutic efficacy. Here we review the major DNA repair pathways and discuss recent advances in the development of novel inhibitors of DNA repair pathways; many of these agents are under preclinical/clinical investigation.

Keywords: DNA repair, Cancer therapy, Chemotherapy and radiotherapy resistance, Small molecule inhibitors

a Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China

b Department of Pharmacology, Zhejiang Medical College, Hangzhou, Zhejiang 310009, China

c Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA

Corresponding author. Tel.: +86 571 87784787; fax: +86 571 7783757.

d These authors contribute equally to this work.

e Tel.: +86 571 87784714.

f Tel.: +86 571 87692678.

g Tel.: +1 617 632 4373.

PII: S0305-7372(09)00093-0

doi:10.1016/j.ctrv.2009.06.005

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