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.
Institute of Molecular Pathology and Immunology of the University of Porto, Portugal.
Sérgia
S
Velho
Giovanni
G
Corso
Carla
C
Oliveíra
Raquel
R
Seruca
D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair / Q000502:physiology; D044127:Epigenesis, Genetic / Q000502:physiology; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D053842:Microsatellite Instability; D008954:Models, Biological; D009154:Mutation / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction / Q000235:genetics; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins