title: EGFR and downstream genetic alterations in KRAS/BRAF and PI3K/AKT pathways in colorectal cancer: implications for targeted therapy.
abstract: The promise of individualized treatment is gradually being fulfilled, and targeted therapy is becoming a powerful strategy to treat selected patients based on their molecular profile. For metastatic colorectal cancer (mCRC) patients anti-EGFR (epidermal growth factor receptor) targeted therapy has markedly improved disease control and survival. However, only a subgroup of patients with mCRC respond to anti-EGFR treatment, and selecting the patients with a positive effect from treatment is important for both the patient and the society. Patients with mutations in the KRAS gene are known as non-responders to anti-EGFR treatment and, consequently, KRAS testing has been employed in routine clinical practice for patient selection. However, a large number of the KRAS wildtype patients do not respond to this treatment. The molecular mechanism underlying response is not fully understood, and other members of the KRAS-BRAF pathway and PI3K-AKT pathway are investigated as predictive biomarkers. Furthermore, concordance of mutation status of primary tumors and their corresponding hepatic or pulmonary metastases, as well as treatment-induced mutations, possess another challenge for properly tailoring the appropriate therapy to this patient group. In this review, molecular biomarkers involved in prediction of response to anti-EGFR treatment are discussed.
authors.affiliation: Department of Surgery, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Marianne
authors.initials: M
authors.lastname: Berg
authors.forename: Kjetil
authors.initials: K
authors.lastname: Soreide
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; D018631:ras Proteins