Modulation of angiogenesis in patients with myelodysplastic syndrome.
Current investigations have revealed that angiogenesis plays a role in the pathogenesis of high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia, and in the mechanisms of disease progression. Secretion of cytokines and growth factors modulates angiogenesis in the marrow leading to increased vascularity and sustenance of the clonal population. For high-risk MDS patients older than 60 years who are not eligible for aggressive chemotherapy or stem cell transplant, there are few therapeutic options other than supportive treatment. Recent delineation of the pathobiology of MDS has resulted in the development of new agents and treatment modalities that impact on these mechanisms. One of the features of bone marrow pathology is the presence of new vessels, which appear to sustain growth and the hypercellularity of the marrow. Blocking angiogenesis may reduce the microvessel density of the marrow, cellularity, and disease progression. Angiogenesis can be targeted by inhibition of vascular endothelial growth factor (VEGF), which modulates new vessel growth, by the use of antibodies aimed at VEGF and its receptors, as well as receptor tyrosine kinases that block VEGF signaling. Other agents include inhibitors of farnesyl transferase and protein kinase C, which affect upstream modulators of growth factors and their receptor interactions; matrix metalloproteinases, which disrupt matrices and adhesion function promoting vessel growth; and other inhibitors with broader function, such as endostatin, thalidomide, and related analogues.
Estey
Elihu H
EH
Section of Acute Leukemia and Myelodysplastic Syndrome, Division of Cancer Medicine, MD Anderson Cancer Center, Box 428, 1515 Holcombe Boulevard, Houston, TX 77030, USA. eestey@mdanderson.org
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D006133:Growth Substances / Q000032:analysis / Q000494:pharmacology; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011379:Prognosis
D020533:Angiogenesis Inhibitors; D006133:Growth Substances