Optimal treatment strategies for localized and advanced microsatellite instability-high colorectal cancer

The defective mismatch repair phenotype (MMR-D) has been recognized as a distinct form of colorectal cancers with specific clinical and biologic features. It is caused by a lack of expression of mismatch repair enzymes in tumor cells either on the basis of hereditary or sporadic mutation of gene(s) encoding the enzymes such as in the Lynch syndrome, or by silencing of gene transcription due to promoter methylation. Colorectal cancers of the MMR-D phenotype have consistently shown to be associated with good prognosis and are likely, at least in early-stage disease, resistant to fluoropyrimidine monotherapy. These characteristics have significant implications for clinical practice and treatment strategies, particularly in the adjuvant setting.