Moffitt researchers identify mechanism of resistance to BRAF inhibitors in melanoma
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TAMPA, Fla. – Melanoma is one of the most aggressive types of skin cancer, but recent advances in targeted therapies have improved the prognosis for many patients. Unfortunately, for some patients these positive outcomes are not long lasting, due to the development of drug resistance and tumor recurrence. Moffitt Cancer Center researchers have discovered a mechanism by which melanoma cells become resistant to the commonly used drugs that target the BRAF protein and its signaling pathway. Their study was published online today by the journal Cancer Research.

One of the most common genetic mutations found in melanoma is alteration of the BRAF gene. Mutations in BRAF are found in approximately 50 percent of all melanomas, leading to increased cell proliferation and survival. Several drugs are available that target BRAF and a downstream gene named MEK that cooperates with BRAF in cancer development. These drugs have resulted in significant improvements in patient outcomes; however, many patients eventually develop drug resistance.

Moffitt researchers conducted a series of laboratory experiments with cell lines and mouse models to determine how melanoma becomes resistant to these commonly used drugs. They discovered that melanoma cells that are resistant to BRAF inhibitors undergo a similar response

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