Anti-angiogenic therapy in uveal melanoma

For several decades, targeting of tumor-related vessels has been regarded as a potential anticancer therapy. Such anti-angiogenic therapy is based on the assumption that a tumor cannot grow beyond the limits of diffusion (about 1-2 mm) of oxygen and nutrients from capillaries, unless angiogenesis takes place. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis, regulating vasopermeability as well as the proliferation and migration of endothelial cells. In several types of cancer (colon carcinoma, soft tissue sarcomas and gastric cancer), serum VEGF levels are a marker for disease stage and an indicator of metastasis. VEGF levels are significantly elevated in uveal melanoma patients with metastatic disease compared to patients without metastases. Anti-angiogenic therapy, such as bevacizumab, is currently used for the treatment of metastases of several malignancies. Anti-angiogenic therapy has not yet been tested for the treatment of primary uveal melanoma or related metastatic disease. Clinicians, however, have a broad experience with anti-angiogenic agents in patients with uveal melanoma by treating the complications of radiation therapy. We will discuss tumor angiogenic processes and related molecular pathways in uveal melanoma. The role of VEGF and the potential use of current commercially and experimentally available anti-angiogenic drugs for the treatment of primary uveal melanoma and/or metastatic disease will be explained below.