Vemurafenib: the road to personalized medicine in melanoma

R N Amaria, K D Lewis, A Jimeno
Drugs of Today 2012, 48 (2): 109-18
Advanced melanoma has a poor prognosis due to its resistance to traditional chemotherapeutics, leading to the search for alternative treatment approaches. With the finding that approximately 50% of melanomas harbor an activating mutation in the serine/threonine-protein kinase B-raf gene (BRAF), inhibition of mutated B-raf represented an attractive and innovative focus for the development of novel targeted therapy potentially benefiting a large proportion of melanoma patients. Impressive response rates with an overall survival benefit in addition to minimal treatment-related toxicity in phase I-III clinical studies led to the FDA's approval of vemurafenib for patients with locally advanced/unresectable or metastatic BRAFV600E-mutated malignant melanoma in August 2011. While the majority of patients with BRAF-mutated disease show favorable treatment responses shortly after initiation of vemurafenib therapy, the median progression-free survival is 6 months, making the search for resistance mechanisms a high priority. While vemurafenib represents an excellent model for successful targeted anticancer therapy, long-term safety data are needed and rational combination with other agents will be critical to prevent or circumvent the development of resistance.

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