Abstract
Adult acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS) remain a formidable therapeutic challenge. Although 30-40% of young adults with AML may have prolonged remissions, following either intensive chemotherapy or bone marrow transplantation, the remainder relapse and ultimately die of their disease. Older adults, or those with leukemia following an antecedent hematologic disorder such as MDS, experience only brief remissions with modern chemotherapy, and in this population the rate of long-term disease-free survival is less than 10%. Treatment of MDS consists mainly of supportive care with antibiotics and transfusion therapy, and only a small minority of patients are cured with allogeneic stem cell transplantation. As the biology of the acute leukemias and MDS has unfolded, new potential targets for arresting malignant cell growth and restoring normal hematopoiesis have been identified. This article will discuss the relevance of the ras-raf signaling pathway in the pathogenesis of myeloid leukemia, and describes some early results in the use of novel small molecule inhibitors of farnysltransferase and raf protein kinase in leukemia therapy.
Keywords: acute myeloid leukemia, myelodysplasia, raf kinase
Current Pharmaceutical Design
Title: Inhibition of Raf Kinase in the Treatment of Acute Myeloid Leukemia
Volume: 8 Issue: 25
Author(s): Michael Crump
Affiliation:
Keywords: acute myeloid leukemia, myelodysplasia, raf kinase
Abstract: Adult acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS) remain a formidable therapeutic challenge. Although 30-40% of young adults with AML may have prolonged remissions, following either intensive chemotherapy or bone marrow transplantation, the remainder relapse and ultimately die of their disease. Older adults, or those with leukemia following an antecedent hematologic disorder such as MDS, experience only brief remissions with modern chemotherapy, and in this population the rate of long-term disease-free survival is less than 10%. Treatment of MDS consists mainly of supportive care with antibiotics and transfusion therapy, and only a small minority of patients are cured with allogeneic stem cell transplantation. As the biology of the acute leukemias and MDS has unfolded, new potential targets for arresting malignant cell growth and restoring normal hematopoiesis have been identified. This article will discuss the relevance of the ras-raf signaling pathway in the pathogenesis of myeloid leukemia, and describes some early results in the use of novel small molecule inhibitors of farnysltransferase and raf protein kinase in leukemia therapy.
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Cite this article as:
Crump Michael, Inhibition of Raf Kinase in the Treatment of Acute Myeloid Leukemia, Current Pharmaceutical Design 2002; 8 (25) . https://dx.doi.org/10.2174/1381612023393008
DOI https://dx.doi.org/10.2174/1381612023393008 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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