KRAS signaling pathway alterations in microsatellite unstable gastrointestinal cancers.

Microsatellite instability (MSI) occurs in about 15% of gastrointestinal cancers and it is associated with specific clinic, pathologic, and molecular features of the tumors. MSI-high (MSI-H) carcinomas also follow specific tumor development pathways. This review is focused on the molecular profile of alterations in members of the KRAS signaling pathway (EGFR, KRAS, BRAF, PIK3CA, RASSF1A, and MLK3 genes) in MSI gastrointestinal carcinomas. Alterations in these genes characterize more than half of gastrointestinal cancers and frequently occur simultaneously in the same tumor, pinpointing the KRAS signaling pathway as one of the most frequently altered pathways in this subset of cancers. Nowadays, many and novel inhibitors targeting molecules of this signaling pathway are being described; therefore, it is worthwhile to test their efficacy in MSI gastrointestinal cancers in order to develop new and more directed targeted therapies for patients affected by this disease.