New insights into the molecular pathogenesis of colorectal cancer.

Although there have been tremendous advances in the management of colorectal cancer (CRC), there is still a need for improved therapeutic approaches. On a molecular genetic level, CRC is one of the best-understood solid malignancies, and these insights can serve as a foundation for the design of novel targeted therapies. We present new genetic and epigenetic pathways that highlight the heterogeneous mechanisms in CRC pathogenesis, including the roles of the MYH DNA repair gene and of aberrant DNA hypermethylation and imprinting. We then describe some of the successful targeted therapies that inhibit COX2, EGFR, and VEGF as well as potential new targets that have been revealed by studies of molecular genetics.