current trends and future directions in clinical trials for malignant melanoma treatment using anti-angiogenic strategies当前的趋势和未来方向使用抗血管生成治疗恶性黑色素瘤的临床试验策略.pdfVIP

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current trends and future directions in clinical trials for malignant melanoma treatment using anti-angiogenic strategies当前的趋势和未来方向使用抗血管生成治疗恶性黑色素瘤的临床试验策略.pdf

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current trends and future directions in clinical trials for malignant melanoma treatment using anti-angiogenic strategies当前的趋势和未来方向使用抗血管生成治疗恶性黑色素瘤的临床试验策略

Journal of Cancer Therapy, 2012, 3, 312-320 /10.4236/jct.2012.34040 Published Online August 2012 (http://www.SciRP.org/journal/jct) Current Trends and Future Directions in Clinical Trials for Malignant Melanoma Treatment Using Anti-Angiogenic Strategies Daemon Dewing1,2,3*, Rowan Pritchard Jones3,4 1Department of Burns Plastic Surgery, Whiston Hospital, Prescott, UK; 2Department of Plastic Surgery, Whiston Hospital, Pres- 3 cott, UK; Mersey Academic Plastic Surgery Group, Liverpool Cancer Research UK Centre, Department of Molecular and Clinical Cancer Medicine, The Duncan Building, Liverpool, UK; 4Department Plastic Surgery, The Christie NHS Foundation Trust, Man- chester, UK. * Email: daemon.dewing@ Received June 12th, 2012; revised July 15th, 2012; accepted July 28th, 2012 ABSTRACT 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 metas- tatic 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, ul- ceration and increased rate of relapse. Melanoma cells secrete several pro-angiogenic cytokines including Vascular En- dothelial 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