Current Trends and Future Directions in Clinical Trials for Malignant Melanoma Treatment Using Anti-Angiogenic Strategies

摘要

Melanoma is the most lethal skin cancer with a high propensity to metastasis and conventionally is poorly responsive to non-surgical treatments including chemotherapy and radiotherapy. Considerable advances have been made recently targeting BRAF mutations and immune regulation and, for the first time, credible options exist for patients with metastatic disease. Angiogenesis, the growth of new blood vessels, is an absolute prerequisite for tumour growth beyond a few millimetres in size. Melanoma neovascularisation is correlated with poor prognosis, reduced overall survival, ulceration and increased rate of relapse. Melanoma cells secrete several proangiogenic cytokines including Vascular Endothelial Growth Factor VEGF-A and raised levels of expression are associated with the switch from indolent radial, to invasive vertical and then metastatic growth phases. Understanding the processes underlying angiogenesis and how it relates to tumour growth broadly and to melanoma specifically is instrumental in the current drive to develop new treatments that target a range of tumour cell receptors and intracellular processes from receptor antagonism to monoclonal antibodies aimed at the disruption of the process of tumour angiogenesis. We discuss recent and current trials for metastatic melanoma therapy, and discuss potential directions of future treatment scheduling considering different treatment scheduling approaches beyond the parameters of standard drug trials.