Chemotherapy of MMR-deficient colorectal cancer

Colorectal cancer (CRC) continues to rank as the third most common cancer in Western society and the second leading cause of cancer death in North America. There are at least three distinct, and relatively discreet, molecular pathways associated with this disease: chromosomal instability (CIN), microsatellite instability (MSI) and the cytosine polyguanine island methylator phenotype. Defects in the DNA mismatch repair system (MMR) account for the MSI phenotype and genotype of about 15 % of CRC. Although high frequency MSI tumors have better stage independent prognosis compared to those with CIN, MMR deficient CRC appears to be resistant to fluorouracil based treatment, but sensitive to other therapeutic regimens. This review summarises current literature on differential chemosensitivity of MMR-deficient CRC.