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Targeting the Double-Strand DNA Break Repair Pathway as a Therapeutic Strategy

Authors' Affiliations: ¹ The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, United Kingdom and ² Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom

Requests for reprints: Alan Ashworth, The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom. Phone: 44-20-7153-5333; Fax: 44-20-7153-5340; E-mail: alan.ashworth{at}icr.ac.uk.

Abstract

DNA repair pathways are crucial for the maintenance of genome integrity. The pathway that repairs DNA double-strand breaks (DSB) has components involved in both signaling and repairing DNA damage. Impairing DSB repair using specific inhibitors of signaling or repair might, in principle, sensitize tumor cells to particular DNA-damaging agents. Moreover, the existence of specific defects in DNA repair pathways in tumors provides the rationale for the use of "synthetic lethal" approaches targeting this cellular "Achilles' heel." Here, we discuss the mechanisms involved in DSB repair and detail potential therapeutic approaches based on targeting this pathway.

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