Predictive role of DNA repair genes in tumor response to chemotherapy

In the last years both the molecular characterization of human tumours and the unravelling of the mechanisms of action of the anticancer agents and of the pathways involved in the repair of the lesions they cause, have open up the possibility to tailor the treatment of cancer. The cytotoxicity of both chemotherapy and radiotherapy is to a large extent directly related to their ability to induce DNA damage. In addition, it has been demonstrated that increased DNA-repair activity in tumour cells is associated to resistance to treatment to DNA-directed drugs, while defects in DNA repair pathways results in hypersensitivity to these agents. The definition of sub-sets of patients whose tumors harbour specific molecular characteristics that would render them sensitive/resistant to a given treatment is an urgent medical need, as it would avoid unsuccessful and toxic treatment. We will here discuss and review the preclinical and clinical evidence of the role of genes involved in nucleotide excision repair and mismatch repair in predicating the response to alkylating agents, methylating agents and antimetabolites based chemotherapy in human tumors.