Researchers have identified a compound that could prevent malignant melanoma cells from spreading throughout the body. If the compound is successfully developed into a human drug, it has the potential to prevent the majority of deaths caused by metastases from this cancer.
The study, “Pharmacological inhibition of Myocardin-related transcription factor pathway blocks lung metastases of RhoC overexpressing melanoma,” was published in the journal Molecular Cancer Therapeutics.
Earlier studies have suggested that a molecular signaling pathway, known as Rho pathway, is involved in melanoma metastasis formation. Researchers at Michigan State University studied the molecular events triggering spread of cancer in two types of lab-grown human melanoma cells.
One of them was highly metastatic, while the other was more benign. It turned out that, compared to the benign cells, the more aggressive cell type had high activity of a key factor in the Rho pathway. In these cells, researchers also noted that a factor related to the Rho pathway, called MRTF (Myocardin-related transcription factor), was more active.
MRTF, activated by the Rho pathway, is a factor that can turn on genes. The research team found that these genes are crucial for the cells’ ability to migrate.
When the team tested a previously developed compound, which prevents MRTF from doing its job, it reduced the ability of the aggressive cells to move by up to 90%.
Then, when testing the compound in mice that had been injected with human melanoma cells, the compound reduced both the number and size of lung metastases.
“It’s been a challenge developing small-molecule drugs that can block this gene activity that works as a signaling mechanism known to be important in melanoma progression,” Richard Neubig, MD, PhD, pharmacology professor and senior study author, said in a press release.
The research team is now trying to figure out a way to test which patients exhibit high activity of the Rho pathway. “The effect of our compounds on turning off this melanoma cell growth and progression is much stronger when the pathway is activated,” said study co-author Kate Appleton, PhD. “We could look for the activation of the MRTF proteins as a biomarker to determine risk, especially for those in early-stage melanoma.”
“The majority of people die from melanoma because of the disease spreading,” said Neubig. “Our compounds can block cancer migration and potentially increase patient survival.”