TY - JOUR
T1 - K-Ras, Intestinal homeostasis and colon cancer
AU - Goel, Sanjay
AU - Huang, Jie
AU - Klampfer, Lidija
N1 - Publisher Copyright:
© 2015 Bentham Science Publishers.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Activating Ras mutations, present in about 20% of human cancers, compromise the GTPase activity of Ras and therefore trigger accumulation of Ras in the GTP-bound state. Among the three family members, K-Ras, H-Ras and N-Ras, K-Ras is the most frequently mutated gene, with 30-50% of colon cancer patients harboring activating K-Ras mutations. Oncogenic mutations of K-Ras have been found at codons 12, 13, 61 and 146. Activation of Ras triggers constitutive activation of signaling pathways, including the MAPK and AKT pathways, which allows tumor cells to proliferate in the absence of growth factors and increases their survival. In addition, activated Ras triggers inflammation and thus promotes tumor progression in a cell non-autonomous manner. The presence of K-Ras mutations not only has prognostic value, but it also predicts the responsiveness of colon cancer patients to inhibitors of EGFR signaling.
AB - Activating Ras mutations, present in about 20% of human cancers, compromise the GTPase activity of Ras and therefore trigger accumulation of Ras in the GTP-bound state. Among the three family members, K-Ras, H-Ras and N-Ras, K-Ras is the most frequently mutated gene, with 30-50% of colon cancer patients harboring activating K-Ras mutations. Oncogenic mutations of K-Ras have been found at codons 12, 13, 61 and 146. Activation of Ras triggers constitutive activation of signaling pathways, including the MAPK and AKT pathways, which allows tumor cells to proliferate in the absence of growth factors and increases their survival. In addition, activated Ras triggers inflammation and thus promotes tumor progression in a cell non-autonomous manner. The presence of K-Ras mutations not only has prognostic value, but it also predicts the responsiveness of colon cancer patients to inhibitors of EGFR signaling.
KW - Colon cancer
KW - EGFR inhibitors
KW - Inflammation
KW - Ras
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U2 - 10.2174/1574884708666131111204440
DO - 10.2174/1574884708666131111204440
M3 - Article
C2 - 24219000
AN - SCOPUS:84928910796
SN - 1574-8847
VL - 10
SP - 73
EP - 81
JO - Current Clinical Pharmacology
JF - Current Clinical Pharmacology
IS - 1
ER -