Investigational treatment for scleroderma autoimmune disease shows high efficacy in melanoma patients.
The combination of a chemical compound and an investigational drug was found to reduce melanoma metastasis by nearly 90%, and shows promise for future skin cancer treatments.
In a study published in Molecular Cancer Therapeutics, the investigators found that a human-made, small-molecule drug compound attacks the gene’s ability to produce RNA molecules and certain proteins in melanoma tumors.
This transcription process is what allows the cancer to spread, however, the compound is able to shut this down, according to the study.
“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 Richard Neubig. “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 hardening of skin tissues, according to the study. Furthermore, the same mechanisms that cause fibrosis in scleroderma also contributed to cancer metastasis.
“Melanoma is the most dangerous form of skin cancer with around 76,000 new cases a year in the United States,” said co-author Kate Appleton. “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.”
Today, small-molecule drugs comprise more than 90% of drugs on the market.
In the study, the investigators demonstrated how the compounds could stop the proteins, called Myocardin-related transcription factors (MRTFs), from initiating the gene transcription process in melanoma cells. Initially, these triggering proteins are turned on by the protein Ras homology C (RhoC), which is found in the signaling pathway that causes the disease to spread.
The results of the study showed the compound reduced the spread of melanoma cells by 85% to 95%. Furthermore, the potential drug was able to significantly reduce tumors in the lungs of mouse models injected with human melanoma cells.
“We used intact melanoma cells to screen for our chemical inhibitors,” Neubig said. “This allowed us to find compounds that could block anywhere along this RhoC pathway.”
When the compounds blocked the entire path, it allowed the investigators to identify the MRTF signaling protein as a new target.
The authors noted that an important next step in their compound development will be to identify which patients have the RhoC pathway turned on, so they can better determine which patients would gain the greatest benefit from this treatment.
“The effect of our compounds on turning off this melanoma cell growth and progression is much stronger when the pathway is activated,” Appleton. “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 caught early, the risk of death is only 2%, according to the authors. However, if the disease is caught late and it has already metastasized, the percentage increases to 84%.
“The majority of people die from melanoma because of the disease spread,” Neubig said. “Our compounds can block cancer migration and potentially increase patient survival.”