Gene mutation confirmed as a key to treating melanoma
Friday, 11 June, 2010
Doubts about the role played by mutations in the gene BRAF in the development of melanoma have largely been laid to rest by new research which confirms that drugs inhibiting the gene greatly increase chances of survival.
Several drugs targeting the BRAF gene have shown positive results in clinical trials, but it remained unclear whether this might have been due to other effects of the drugs. The high profile failure of BRAF inhibitor sorafenib to improve survival rates of melanoma patients in clinical trials last year raised further questions. However research now published in the journal Science Translational Medicine has shown that sorafenib failed because it doesn’t target the mutated form of BRAF in tumours, while demonstrating that a second generation drug PLX4720 works in melanoma because it does target damaged BRAF.
Researchers constructed models using drug-resistant forms of the BRAF protein, then tested whether the drugs retained their anti-cancer activity on tumour cells with mutated forms of it.
"We have absolutely confirmed that BRAF is an important drug target for malignant melanoma, and that the clinical benefit from these second-generation drugs is due to their ability to target the damaged BRAF protein," says Professor Richard Marais from the UK’s Institute of Cancer Research (ICT). "It is crucial that we understand the mechanism behind these drugs' effects to ensure they are only given to patients with the specific genetic defects - in this case, a mutated BRAF gene - that will allow them to benefit. This knowledge may also help us combat resistance and develop new-generation drugs."
The researchers also noted that drugs targeting BRAF may also be important in treating tumours other than melanoma in which mutations of the protein are common. For instance, BRAF is thought to be mutated in 45 percent of thyroid cancer cases, 13 percent for colorectal cancer and 10 percent for ovarian cancer.
Funding for the research was provided by the ICT and the UK’s Wellcome Trust.
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