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New small molecule shows promise for inhibition of melanoma metastasis

A novel small-molecule drug, initially developed as a potential therapy for scleroderma, has been shown to inhibit melanoma metastasis by as much as 90% in melanoma models.

According to a paper published in Molecular Cancer Therapeutics (Jan. 2017; 16(1)), the molecule—known as CCG-203971—inhibits Rho-activated gene transcription in melanoma cells, interfering with the spread of the cancer.

“It’s been a challenge developing small-molecule drugs that can block this gene activity that works as a signalling mechanism known to be important in melanoma progression,” said Dr. Richard Neubig, a pharmacology professor and co-author of the study, in a press release from Michigan State University in East Lansing.

Testing the drug in two cellular melanoma models, investigators found it was able to stop proteins, known as Myocardin-related transcription factors, or MRTFs, from initiating the gene transcription process in melanoma cells. MRTFs, they note, are first activated by the protein Ras homology C (RhoC), which is part of a signalling pathway that can cause melanoma to aggressively spread. This reduced the migration of the test cells by 85 to 90%.

In a mouse model of melanoma, the compound greatly reduced the appearance of tumours, particularly in the lungs, of animals who had been injected with human melanoma cells.

Co-author Kate Appleton, a postdoctoral student at Michigan State University, said in the release that figuring out which patients have this signalling pathway activated is an important next step, as it would allow them to identify which human patients would benefit most from the new molecule.

“The effect of our compounds on turning off this melanoma cell growth and progression is much stronger when the pathway is activated,” she said. “We could look for the activation of the MRTF proteins as a biomarker to determine risk, especially for those in early-stage melanoma.”

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