Regulation of angiogenesis in malignancies associated with Epstein-Barr virus and Kaposi's sarcoma-associated herpes virus

Abstract

Tumor angiogenesis is the process by which new blood vessels are formed within emerging or progressing malignancies. The human Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus critically contribute to the pathogenesis of selected tumor types, including nasopharyngeal carcinoma and Kaposi's sarcoma, respectively, where angiogenesis is robust and often disrupted. Lymphangiogenesis, the process by which new lymphatic vessels are formed, is also induced in Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus-associated malignancies and in some cases may contribute to metastasis. Recent studies have identified a number of molecules and signaling pathways that underlie angiogenesis and lymphangiogenesis, and clarified the pivotal role of the VEGF family of proteins and their receptors. New treatment modalities that target members of this family have gained approval for clinical use in cancer. Pathogenetic steps are often difficult to dissect in many cancer types, but virus-induced malignancies provide a unique opportunity for understanding the molecular regulation of cancer progression, including angiogenesis. Dissection of viral gene contribution to tumor angiogenesis could result in a better understanding of the angiogenic process, its contribution to cancer and help in the design of rational therapies that target tumor growth and vascularization.