Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

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Targeting the RAS Signaling Pathway in Malignant Hematologic Diseases

Author(s): M. A. Morgan, A. Ganser, C. W. M. Reuter.

Abstract:

Molecularly targeting signaling pathways that are involved in the pathogenesis of hematopoietic malignancies may lead to more specific and efficacious therapies. Activation of the RAS signal transduction cascade is a common feature in the molecular pathogenesis of hematologic malignancies. A number of novel agents targeting RAS signaling have been developed over the past decade. This review will focus on these agents, which include inhibitors of RAS post-translational modification (farnesyl transferase (FTase)-, geranylgeranyl transferase-I (GGTase-I)-, isoprenylcysteine carboxylmethyltransferase (ICMTase)-inhibitors, statins, bisphosphonates), and inhibitors of RAF and MEK activity. Although some of these inhibitors (e.g. FTase, RAF and MEK inhibitors) were developed to specifically inhibit RAS signaling, it has become clear that RAS may not be the only critical target of these compounds. This review provides a background on RAS signaling in hematologic malignancies and discusses opportunities to exploit aberrant cancer cell signaling in order to develop better treatment options for patients suffering from these diseases.

Keywords: Farnesyltransferase inhibitors, geranylgeranyltransferase I inhibitors, RAS signaling, hematologic malignancies

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Article Details

VOLUME: 8
ISSUE: 2
Year: 2007
Page: [217 - 235]
Pages: 19
DOI: 10.2174/138945007779940043
Price: $58