Antiangiogenesis in haematological malignancies.
Angiogenesis, the growth of new capillary blood vessels, is a central regulator of cancer growth, and a validated target for cancer therapy. The antiangiogenic agents in clinical use target one or more cellular pathways involved in the cascade of vascular growth. In haematological malignancies, angiogenesis occurs within a bone marrow ecosystem comprised of closely apposed malignant cells, endothelial cells, pericytes, fibroblasts, endothelial progenitor cells, dendritic cells, and extracellular matrix. Inhibition of angiogenesis therefore blocks not only the delivery of oxygen and micronutrients to cancer cells, but also disrupts the interdependency of these cellular players and the paracrine effects they exert to maintain the malignant phenotype. Agents such as thalidomide, lenalidomide, bortezomib, and bevacizumab, have demonstrated clinical activity in myeloma, myelodysplastic syndrome, and leukaemias. In leukaemia, vascular endothelial growth factor (VEGF) is emerging as a compelling biological target for therapy, as well as a potential predictive marker for disease relapse. Initial clinical studies suggest that the anti-VEGF strategies may advance the primary, sequential or adjunctive treatment for leukaemia, and establish the basis for other potential antiangiogenic strategies in haematological malignancies.
Li
William W
WW
The Angiogenesis Foundation, Cambridge, MA 02138, USA. wli@angio.org
Hutnik
Michelle
M
Gehr
Gerald
G
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A