A large portion of melanoma cases prove fatal because the disease has already progressed beyond treatment options. However, a new study reports that a small-molecule drug can stop the spread of melanoma by as much as 90 percent. Furthermore, the pathway behind this drug’s actions may be developed into a useful biomarker to identify and successfully treat melanoma patients in the early stages.
"Melanoma is the most dangerous form of skin cancer with around 76,000 new cases a year in the United States," said Kate Appleton, co-author of the study, published in Molecular Cancer Therapeutics. "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."
To fight the spread of melanoma, Appleton and her colleagues turned to a small molecule drug that showed promise against another skin-related disease known as scleroderma.
"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 Richard Neubig, a pharmacology professor and the study’s senior author. "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 autoimmune rheumatic disease that hardens the skin and affects other vital organs.
In particular, Neubig and his team reported that treatment of this compound seemed to stop melanoma’s spread by 85 to 90 percent. Mice injected with melanoma cells also showed smaller tumors with exposure to this drug.
They credit the anticancer effects to the molecule’s ability to inhibit a protein known as Myocardin-related transcription factor (MRTF). This protein normally initiates genetic transcription in cancer cells. Blocking it may prevent the spread of aggressive melanoma throughout the body.
Importantly, the anticancer effects of this compound was most significant in melanomas with this pathway activated. "The effect of our compounds on turning off this melanoma cell growth and progression is much stronger when the pathway is activated," Appleton explained. This knowledge could be applied towards the development of diagnostic tests to detect early melanoma presence as well as identify patients who would best respond to the drug. "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." Neubig stressed that, for melanoma, early detection and treatment is key, as the mortality rate rises from 2 percent if the disease is caught early versus a staggering 84 percent if the disease is caught late.
Additional sources: Michigan State University