Editorial [ DNA Repair as a Target for Anti-Cancer Therapy Guest Editor: Robert M. Brosh Jr. ]

A number of human proteins have been characterized which have important roles in pathways responsible for sensing, responding, and repairing DNA damage. Collectively, these proteins are referred to as DNA repair or DNA damage response proteins, but their functions are specific in terms of pathways that can be potentially manipulated to modulate the biological response to a given cytotoxic agent. Selective inactivation of a DNA repair pathway may enhance existing or developing anticancer therapies. The scope of this Hot Topics series will be to discuss DNA repair proteins that can be targeted to improve cancer therapeutic approaches. A collection of review articles is presented that provides a unique prospective of discussing emerging concepts and strategies to fight cancer through DNA repair inhibition. Treatment with anti-cancer drugs such as small molecule compounds that modulate the expression or activity of a DNA repair protein in specific DNA damage response pathways is proposed to represent a viable approach to selectively kill cancer cells exposed to DNA damaging chemotherapy or radiation. DNA repair proteins that may be suitable targets for fighting cancer are diverse and involve steps of pathways from a variety of DNA repair processes. An overview of DNA repair proteins as molecular targets for cancer therapeutics and discussion of results from experimental studies providing proof-of-concept is addressed by Drs. M. Kelley and M. Fishel. Dr. M. Bignami and colleagues discuss the role of mismatch repair and O6-methylguanine-DNA-methyltransferase in the response to anticancer therapies. Inhibition of specific base excision repair proteins to improve the efficacy of current cheomotherapy strategies is presented in the review by Dr. R. Roy and co-workers. Drs. G. Maga and U. Hübscher present translesion DNA polymerases as a novel target for anti-cancer drugs. Rationale for the development of Tyrosyl-DNA phophosphodiesterase 1 inhibitors is offered by Dr. Y. Pommier and colleagues. Cancer therapy mediated by polynucleotide kinase inhibitors is discussed by Drs. J.N.M. Glover, M. Weinfeld and colleagues. Drs. A.S. Balajee and E.T. Sakamoto Hojo review the prospect of targeting Poly(ADP) ribose polymerase and interacting proteins for cancer treatment. Dr. S. Cantor and colleagues evaluate the evidence that the BRCA-FA pathway is a promising target for anti-tumor drugs. Drs. S. Powell and L. Kachnic elaborate on the therapeutic exploitation of tumor cell defects in homologous recombination. Drs. R. Gupta and R. Brosh propose that helicasedependent DNA repair pathways represent a viable approach to kill cancer cells. Collectively, this Hot Topics review series provides a timely discussion of how DNA repair proteins engaged in distinct pathways of DNA maintenance represent viable candidates for improving the efficacy of anti-cancer therapies.