Cancer genetics of sporadic colorectal cancer: BRAF and PI3KCA mutations, their impact on signaling and novel targeted therapies.
Novel activating mutations in sporadic colorectal cancer (CRC) have recently been identified on major kinase encoding genes such as BRAF and PI3KCA. The presence of these activating point mutations, including the well characterized KRAS oncogene mutations, represent up to 75% of cases in CRC. These genes, that have been implicated in the adenoma-carcinoma transition, cause deregulation and constitutive activation of the MAP AKT/kinase pathways, rendering growth advantages to colon tumor cells. This review focuses on the key genetic alterations underlying the cumulative effect of multiple mutations within the colon cancer cell. Moreover, the currently available and alternative treatment approaches that may target these different genetic alterations are discussed, such as the novel BRAF inhibitor. Identification of novel mutations as well as differential gene expression analyzed by microarray reveal potential targets for combined therapeutic protocols which will result in personalized treatments in the near future.
Oikonomou
Eftychia
E
Laboratory of Signal Mediated Gene Expression, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Pintzas
Alexandros
A
D000818:Animals; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D015398:Signal Transduction
D019869:Phosphatidylinositol 3-Kinases; D048493:Proto-Oncogene Proteins B-raf