Abstract
Ras is a 21 kDa membrane-localized G protein that is coupled to receptor and non-receptor tyrosine kinase activation of downstream cytoplasmic and nuclear events. Mutated ras genes are common, and occur in a wide variety of human malignancies. These activating mutations result in constitutive signaling, thereby stimulating cell proliferation and inhibiting apoptosis. Preclinically, inhibitors of ras signaling revert ras-dependent cellular transformation, and cause regression of ras-dependent rodent tumor xenografts. The ras signaling pathway has therefore attracted considerable attention as a target for anticancer therapy. In this review, novel therapeutic approaches based on the inhibition of ras-mediated signaling, are described. The discussion will be limited to inhibitors which are currently in human clinical trials, and include inhibitors of ras processing, inhibitors of ras protein synthesis and inhibitors of downstream ras effectors.
Current Pharmaceutical Design
Title: Ras Signaling Pathway Proteins as Therapeutic Targets
Volume: 7 Issue: 16
Author(s): Alex A. Adjei
Affiliation:
Abstract: Ras is a 21 kDa membrane-localized G protein that is coupled to receptor and non-receptor tyrosine kinase activation of downstream cytoplasmic and nuclear events. Mutated ras genes are common, and occur in a wide variety of human malignancies. These activating mutations result in constitutive signaling, thereby stimulating cell proliferation and inhibiting apoptosis. Preclinically, inhibitors of ras signaling revert ras-dependent cellular transformation, and cause regression of ras-dependent rodent tumor xenografts. The ras signaling pathway has therefore attracted considerable attention as a target for anticancer therapy. In this review, novel therapeutic approaches based on the inhibition of ras-mediated signaling, are described. The discussion will be limited to inhibitors which are currently in human clinical trials, and include inhibitors of ras processing, inhibitors of ras protein synthesis and inhibitors of downstream ras effectors.
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Cite this article as:
Alex A. Adjei , Ras Signaling Pathway Proteins as Therapeutic Targets, Current Pharmaceutical Design 2001; 7 (16) . https://dx.doi.org/10.2174/1381612013397258
DOI https://dx.doi.org/10.2174/1381612013397258 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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