Investigational Drug Stops 90% of Melanoma Metastases

Findings from a new study suggest that an investigational small-molecule compound could decrease the spread of melanoma by 90%.

This drug candidate attacks a gene’s ability to create RNA and certain proteins associated with melanoma. This gene transcription process typically causes metastasis, but the new drug has shown the ability to prevent it, according to a study published by Molecular Cancer Therapeutics.

There have been limited other compounds that are able to elicit these effects, the study authors noted.

“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,” said co-author of the study Richard Neubig, MD, PhD. “Our chemical compound is actually the same one that we’ve been working on to potentially treat the disease scleroderma, which now we’ve found works effectively on this type of cancer.”

Scleroderma is a rare autoimmune disease that causes the skin and other tissues to harden, similar to the process of fibrosis. Scleroderma can also aid cancer metastasis.

These early findings suggest that this novel drug could be effective treating the aggressive skin cancer, which causes approximately 10,000 deaths per year, according to the study.

“Melanoma is the most dangerous form of skin cancer with around 76,000 new cases a year in the United States,” said the study’s co-author Kate Appleton, PhD. “One reason the disease is so fatal is that it can spread throughout the body very quickly and attack distant organs such as the brain and lungs.”

The authors discovered that the investigational compound was able to inhibit Myocardin-related transcription factor proteins from initiating gene transcription in melanoma calls, according to the study. These proteins are typically activated by the RhoC protein, which can cause aggressive metastasis.

The compound was able to reduce the spread of cancer cells up to 90%, and was also able to reduce tumors in lungs of mice models that were injected with melanoma cells.

“We used intact melanoma cells to screen for our chemical inhibitors,” Dr Neubig said. “This allowed us to find compounds that could block anywhere along this RhoC pathway.”

Inhibiting this pathway allowed the investigators to discover the MRTF protein as a potential new target. An important next step is to discover which patients have this pathway turned on, since it would determine who would benefit the most, according to the study.

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

If melanoma is diagnosed early, the mortality rate is only 2%, but if it is discovered later, the mortality rate skyrockets to 84%. Early detection to prevent metastasis is critical for the survival of patients, and this novel compound could also increase survival.

“The majority of people die from melanoma because of the disease spreading,” Dr Neubig concluded. “Our compounds can block cancer migration and potentially increase patient survival.”