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

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. (C) 2009 Elsevier Ltd. All rights reserved.