Abstract
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.
Keywords: Colon cancer, EGFR inhibitors, inflammation, Ras.
Current Clinical Pharmacology
Title:K-Ras, Intestinal Homeostasis and Colon Cancer
Volume: 10 Issue: 1
Author(s): Sanjay Goel, Jie Huang and Lidija Klampfer
Affiliation:
Keywords: Colon cancer, EGFR inhibitors, inflammation, Ras.
Abstract: 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.
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Cite this article as:
Goel Sanjay, Huang Jie and Klampfer Lidija, K-Ras, Intestinal Homeostasis and Colon Cancer, Current Clinical Pharmacology 2015; 10 (1) . https://dx.doi.org/10.2174/1574884708666131111204440
DOI https://dx.doi.org/10.2174/1574884708666131111204440 |
Print ISSN 1574-8847 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3938 |
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