METHODS FOR REDUCING MICROSATELLITE INSTABILITY INDUCED BY CHEMOTHERAPY AND METHODS FOR SCREENING ANTIOXIDANTS THAT SUPPRESS DRUG-INDUCED MICROSATELLITE INSTABILITY WHILE ENHANCING THE CYTOTOXICITY OF CHEMOTHERAPEUTIC AGENTS
A therapeutic approach to prevent drug resistance and chemotherapy-related secondary cancer associated with DNA mismatch repair (MMR) deficiency is disclosed based on screening antioxidants for reducing microsatellite instability (MSI) while enhancing the cytotoxicity of chemotherapeutic agents. The work is based on experiments using antioxidants to target reactive oxygen species generated by oxaliplatin, a commonly used chemotherapeutic agent, and is applicable to other chemotherapeutic agent, and in particular 5-fluorouracil, methotrexate, CCNU, etoposide and vinblastine. In particular oxaliplatin is co-treated with an antioxidant, including CDC, CAPE, ciclopirox ethanolamine, hinokitiol, gossypol, n-Octyl caffeate, baicalein, or curcumin.
