Targeting DNA Repair Proteins: A Promising Avenue for Cancer Gene Therapy

Jean-Philippe      Belzile; Sibgat   A.   Choudhury; Denis      Cournoyer; Terry   Y.-K.   Chow

doi:10.2174/156652306775515538

Abstract

Enhanced DNA repair in many cancer cells can be correlated to the resistance to cancer treatment, and thus contributes to a poor prognosis. Ionizing radiation and many anti-cancer drugs induce DNA double-strand breaks (DSBs), which are usually regarded as the most toxic types of DNA damages. Repair of DNA DSBs is vital for maintaining genomic stability and hence crucial for survival and propagation of all cellular organisms. Therefore, reducing the capacity of cancer cells to repair DSBs could sensitize tumors to radio/chemotherapy. Many investigators have used gene therapy strategies to down-regulate or inactivate proteins involved in the repair of DSBs in order to reduce the survival of cancer cells. Herein, are reviewed several protein candidates that have been targeted by different gene therapy approaches. Results obtained from in vitro and in vivo experiments are presented and discussed in the perspective of potential gene therapy clinical trials.

Keywords: Antisense, siRNA, radiosensitization, ionizing radiation, chemotherapy, NHEJ, homologous recombination, double-strand break