Jade Homsi1, Adil I Daud. 1. Cutaneous Oncology Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. adil.daud@ moffitt.org.
Abstract
BACKGROUND: Angiogenesis plays an important role in tumor growth and metastasis. METHODS: We review the function of the vascular endothelial growth factor (VEGF) in vessel formation that is complemented by platelet-derived growth factor (PDGF). We also review the agents designed to target VEGF, PDGF, and/or their receptors. RESULTS: VEGF plays a central role in tumor angiogenesis. It is expressed at increased levels in colorectal, liver, lung, thyroid, breast, as well as in bladder, ovary, uterine cancers, and in angiosarcomas, germ cell tumors, intracranial tumors, and others. VEGF blockade has been shown to have a direct and rapid antivascular effect in both animal and human tumors, through deprivation of tumor vascular supply and inhibition of endothelial proliferation. Overexpression of PDGFs and their receptors has also been reported in many types of cancers such as prostate, ovarian, and non-small-cell lung cancer. Many VEGF and PDGF inhibitors are available. The use of some of these inhibitors has significantly improved the survival of cancer patients. Several agents are in development and currently are being tested in clinical trials. CONCLUSIONS: Angiogenic agents inhibiting VEGF and PDGF have shown promising clinical results. Targeting more than one pathway by combining different agents may increase the antitumor activity of these drugs. The implementation of reliable radiologic and pathologic angiogenesis monitoring techniques is necessary to implement antiangiogenic therapies in cancer.
BACKGROUND: Angiogenesis plays an important role in tumor growth and metastasis. METHODS: We review the function of the vascular endothelial growth factor (VEGF) in vessel formation that is complemented by platelet-derived growth factor (PDGF). We also review the agents designed to target VEGF, PDGF, and/or their receptors. RESULTS:VEGF plays a central role in tumor angiogenesis. It is expressed at increased levels in colorectal, liver, lung, thyroid, breast, as well as in bladder, ovary, uterine cancers, and in angiosarcomas, germ cell tumors, intracranial tumors, and others. VEGF blockade has been shown to have a direct and rapid antivascular effect in both animal and humantumors, through deprivation of tumor vascular supply and inhibition of endothelial proliferation. Overexpression of PDGFs and their receptors has also been reported in many types of cancers such as prostate, ovarian, and non-small-cell lung cancer. Many VEGF and PDGF inhibitors are available. The use of some of these inhibitors has significantly improved the survival of cancerpatients. Several agents are in development and currently are being tested in clinical trials. CONCLUSIONS: Angiogenic agents inhibiting VEGF and PDGF have shown promising clinical results. Targeting more than one pathway by combining different agents may increase the antitumor activity of these drugs. The implementation of reliable radiologic and pathologic angiogenesis monitoring techniques is necessary to implement antiangiogenic therapies in cancer.
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