New compound could fight off aggressive melanoma

Cancer
New research, appearing in the journal Cell, reveals a drug compound that could halt the growth of an aggressive form of melanoma.
physician examining mole
If successful in human clinical trials, a new compound may effectively block the growth of melanoma.

Melanoma is a type of skin cancer that accounts for 1 percent of all skin cancer cases. Despite this small percentage, melanoma is responsible for a large number of skin cancer deaths.

According to the American Cancer Society, over 96,000 people in the United States will develop melanoma in 2019, and more than 7,000 will die as a result.

A mutation in a gene that scientists call NRAS causes one form of melanoma to be particularly aggressive. Normally, the NRAS gene encodes a protein of the same name that is mainly involved in regulating cell division.

However, NRAS is an oncogene, meaning that when it mutates, it has the ability to turn normal cells into cancerous cells. Melanoma with NRAS mutations accounts for 20–30 percent of all melanoma cases.

New research may have found a drug compound that could fight off this type of skin cancer. Rutao Cui, a Boston University School of Medicine professor of pharmacology and dermatology, is the last and corresponding author of the study.

Prof. Cui explains the motivation for the research, saying, “There are immunotherapies and targeted therapies that have shown huge improvements for patients with melanoma.

“However, for patients with NRAS mutations, they don’t have very useful or very effective treatment strategies.”

The role of the STK19 gene

In the search for such an effective treatment, the researchers examined the “chain reaction” of genes — and their respective proteins — that trigger melanoma with NRAS mutations.

NRAS “acts like a genetic switch” that is, in turn, turned on and off by other molecules. As Prof. Cui and team explain, until now researchers did not know precisely which proteins trigger NRAS.

However, after performing a series of experiments where they tested the effect of various proteins on NRAS activity, the scientists narrowed their search down to a protein called STK19.

Alterations in the gene that encodes STK19 were present in 25 percent of all human melanomas, write the authors.

They believe that STK19 switches NRAS “on,” which, in turn, activates other genes. Importantly, they could easily deactivate STK19, unlike NRAS.

STK19 inhibitor stops melanoma growth

Prof. Cui and the team then went further. They designed an STK19 inhibitor and tested it both in vitro and in vivo.

Both cell cultures and animal models revealed that the compound — called “ZT-12-037-01” — can inhibit NRAS and stop melanoma from growing.

“Together, our findings provide a new and viable therapeutic strategy for melanomas, harboring NRAS mutations,” conclude the authors.

Next, Prof. Cui and team plan to test their compound with human clinical trials. Until the results of such trials, hopefully, prove that the compound is effective in humans, we need more precisely targeted preventive measures against melanoma, caution the scientists.

“We need more monitoring for early diagnosis and full-body examinations for problematic spots,” says Prof. Cui, “and more proactive strategies for patients [at the highest risk of developing melanoma] to prevent cancer progression and metastasis.”

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