Angiogenesis in melanoma.
The process of angiogenesis is crucial for progression and metastasis of the majority of solid tumors including melanomas. The current review summarizes existing knowledge of the mechanisms of angiogenesis in melanoma, as well as current anti-angiogenic therapeutic strategies and their targets. We focus primarily on the role of key growth factors that are secreted by melanoma cells and known to trigger angiogenic responses, and their receptors as expressed on both endothelial and melanoma cells. Many of these growth factors function in synergy with receptors for extracellular matrix, integrins, and matrix metalloproteinases (MMPs). All of these systems of molecules are activated during major stages of angiogenesis such as endothelial migration, proliferation, and reorganization of surrounding extracellular matrix. The blockade of these molecules and their downstream pathways leads to inhibition of melanoma vascularization. Thus, these classes of molecules are essential for melanoma angiogenesis and, therefore, might serve as promising targets for therapeutic intervention. Many recently developed compounds targeting key pathways in angiogenesis are in their final stages of clinical trials.
Mahabeleshwar
Ganapati H
GH
Department of Molecular Cardiology, J.J. Jacobs Center for Thrombosis and Vascular Biology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Byzova
Tatiana V
TV
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008545:Melanoma / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D012878:Skin Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; D061965:Matrix Metalloproteinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D020782:Matrix Metalloproteinases