Experimental Melanoma Drug Shows Promise

Next generation drug shows anti-cancer activity in 10 of 11 tumor samples during lab tests.

An experimental drug for the treatment of melanoma exhibited promising results treating the disease during lab tests.

In a study published online on November 11, 2014 in the journal Molecular Cancer Therapeutics, the next generation drug TAK-733, a small molecule inhibitor of MEK1/2, exhibited anti-cancer activity in 10 out of 11 tumor samples that were grown in mice. The drug was originally conceived as a second-generation inhibitor in patients carrying the BRAF mutation, however, researchers found the drug to be active in melanoma models regardless of the status of the BRAF mutation status.

Tumors that were treated shrunk up to 100%, the study found.

"The importance of this molecule is that it's a next-generation and highly potent inhibitor of a known melanoma pathway,” said lead author John Tentler, PhD, in a press release. “It was highly effective against melanoma and the method of our study -- using patient-derived tumor samples grown in mice -- makes us especially optimistic that we should see similar results in the human disease.”

Between 50 and 60% of melanomas carry an activating mutation in the gene BRAF. The FDA approved the drug vemurafenib to treat the BRAF-mutant melanoma in 2011, which has response rates of approximately 80% in patients with the BRAF mutation, however, the duration of response is often limited to between a range of 2 to 18 months.

"We're learning how to use existing drugs better, for example RAF along with MEK inhibitors to block both mutations and thus a common mechanism of resistance,” Tentler said. “But there is also room for improvement in the drugs themselves and we hope that TAK-733 could improve on the results of existing, approved MEK inhibitors.”

BRAF inhibitors like vemurafenib and MEK inhibitors such as trametinib have exhibited efficacy in treating melanoma, however, TAK-733 may offer improvements that are substantial enough to justify continued development.

"There's always a need for better, more potent molecules," Tentler said.