Paradigms of vascularization in melanoma : clinical significance and potential for therapeutic targeting

Abstract

Melanoma is the most aggressive form of skin cancer. Malignant melanoma in particular has a poor prognosis and although treatment has improved, drug resistance continues to be a challenge. Angiogenesis, the formation of blood vessels from existing microvessels, precedes the progression of melanoma from a radial growth phase to a malignant phenotype. In addition, melanoma cells can form networks of vessel-like fluid conducting channels through vasculogenic mimicry (VM). Both angiogenesis and VM have been postulated to contribute to the development of resistance to treatment and to enable metastasis. Also, the metastatic spread of melanoma is highly dependent on lymphangiogenesis, the formation of lymphatic vessels from pre-existing vessels. Interestingly, the design and clinical testing of drugs that target VM and lymphangiogenesis lag behind that of angiogenesis inhibitors. Despite this, antiangiogenic drugs have not significantly improved the overall survival of melanoma patients, thus necessitating the targeting of alternative mechanisms. In this article, I review the roles of the three paradigms of tissue perfusion, namely, angiogenesis, VM and lymphangiogenesis, in promoting melanoma progression and metastasis. This article also explores the latest development and potential opportunities in the therapeutic targeting of these processes.