title: Inhibitors of signaling in myelodysplastic syndrome.
abstract: Treatment of myelodysplastic syndrome (MDS) has been hampered by the lack of understanding of the molecular and biological abnormalities associated with this disease. Biological abnormalities may lead to typical phenotypic changes in more differentiated cells. Recent developments in the natural history and underlying molecular mechanisms of MDS and acute myeloid leukemia (AML) have identified new molecular therapeutic targets. Several new classes of drugs have shown promise in early clinical trials and may alter the standard of care of these patients. Among these new drugs are farnesyltransferase inhibitors, receptor tyrosine kinase inhibitors, protein kinase C inhibitors, and VEGF inhibitors. These agents have been tested in patients with solid tumors and hematological malignancies such as AML and MDS. Most of the studies in MDS are in early stages of development, where doses are being determined based on the experience in refractory or relapsed AML or solid tumors. Future therapies in MDS will attempt to resolve cytopenias, eliminate malignant clones and allow differentiation by attacking specific mechanisms of the disease.
authors.affiliation: Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Cancer Research Building 288, 1650 Orleans Street, Baltimore, MD 21231-1000, USA. gorest@jhmi.edu
authors.forename: Steven D
authors.initials: SD
authors.lastname: Gore
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051231:Farnesyltranstransferase; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D020794:Receptor Protein-Tyrosine Kinases