Vascular endothelial growth factor and its receptor as drug targets in hematological malignancies.
Angiogenesis is defined as formation of new blood vessels from the preexisting vasculature, a process which is essential for malignant tumor growth. While this has been accepted for solid forms of cancer there is now emerging evidence that progression of hematological malignancies also requires the induction of new blood vessels. Vascular endothelial growth factor (VEGF) is known to be an essential regulator of physiological and pathological angiogenesis. Numerous preclinical and clinical studies have validated VEGF as target for antiangiogenesis and anticancer therapy. With regard to hematological malignancies a stimulating effect of VEGF for proliferation, survival and migration of leukemia cells could be demonstrated. Bone marrow of leukemia patients shows an increased microvessel density as well as VEGF expression. Complete remissions in acute myeloid leukemia (AML) have been reported by targeting the receptor tyrosine kinase system of VEGF. While the pathophysiology behind the contribution of VEGF to leukemia progression is not yet completely understood, VEGF and its receptors may provide promising targets not only in solid tumors but also hematological malignancies such as AML.
Kessler
Torsten
T
Department of Medicine/Hematology and Oncology, and the IZKF Muenster, University of Muenster, Albert-Schweitzer-Strasse 33, D-48129 Muenster, Germany.
Fehrmann
Frauke
F
Bieker
Ralf
R
Berdel
Wolfgang E
WE
Mesters
Rolf M
RM
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation; D002470:Cell Survival; D018450:Disease Progression; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D040262:Receptors, Vascular Endothelial Growth Factor / Q000187:drug effects* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects* / Q000502:physiology
D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor