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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Reuter, C. W. M. Articles by Bergmann, L. Search for Related Content PubMed PubMed Citation Articles by Reuter, C. W. M. Articles by Bergmann, L. Related Collections Neoplasia Oncogenes and Tumor Suppressors Review Articles Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 September 2000, Vol. 96, No. 5, pp. 1655-1669 REVIEW ARTICLE Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies? Christoph W. M. Reuter, Michael A. Morgan, and Lothar Bergmann From the Department of Internal Medicine III (Hematology and Oncology), University of Ulm, Ulm, Germany. A series of alterations in the cellular genome affecting the expression or function of genes controlling cell growth and differentiation is considered to be the main cause of cancer. These mutational events include activation of oncogenes and inactivation of tumor suppressor genes. The elucidation of human cancer at the molecular level allows the design of rational, mechanism-based therapeutic agents that antagonize the specific activity of biochemical processes that are essential to the malignant phenotype of cancer cells. Because the frequency of RAS mutations is among the highest for any gene in human cancers, development of inhibitors of the Ras-mitogen-activated protein kinase pathway as potential anticancer agents is a very promising pharmacologic strategy. Inhibitors of Ras signaling have been shown to revert Ras-dependent transformation and cause regression of Ras-dependent tumors in animal models. The most promising new class of these potential cancer therapeutics are the farnesyltransferase inhibitors. The development of these compounds has been driven by the observation that oncogenic Ras function is dependent upon posttranslational modification, which enables membrane binding. In contrast to many conventional chemotherapeutics, farnesyltransferase inhibitors are remarkably specific and have been demonstrated to cause no gross systemic toxicity in animals. Some orally bioavailable inhibitors are presently being evaluated in phase II clinical trials. This review presents an overview on some inhibitors of the Ras signaling pathway, including their specificity and effectiveness in vivo. Because Ras signaling plays a crucial role in the pathogenesis of some hematologic malignancies, the potential therapeutic usefulness of these inhibitors is discussed. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Akagi, S. Ogawa, M. Dugas, N. Kawamata, G. Yamamoto, Y. Nannya, M. Sanada, C. W. Miller, A. Yung, S. Schnittger, et al. Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype Haematologica, February 1, 2009; 94(2): 213 - 223. [Abstract] [Full Text] [PDF] M. Raponi, J. E. Lancet, H. Fan, L. Dossey, G. Lee, I. Gojo, E. J. Feldman, J. Gotlib, L. E. Morris, P. L. Greenberg, et al. A 2-gene classifier for predicting response to the farnesyltransferase inhibitor tipifarnib in acute myeloid leukemia Blood, March 1, 2008; 111(5): 2589 - 2596. [Abstract] [Full Text] [PDF] J.-L. Harousseau, J. E. 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