(Boston)--There have been great advances in treating melanoma over the past five years, however, even with these treatments many patients quickly develop drug resistance and die from their disease. A new study from Boston University School of Medicine (BUSM) has discovered that a drug (YK-4-279) that was previously created to target one specific type of protein has much broader use against a family of proteins that act to promote melanoma.
"We find that this drug inhibited melanoma from becoming more aggressive in human cells and in experimental models. We also found a specific pathway that this drug acts through to be anti-cancer: inhibiting proteins that drive genes that promote cancer cell growth and metastasis," explained corresponding author Deborah Lang, PhD, associate professor of dermatology at BUSM.
Melanoma is an aggressive cancer type, with a high propensity for invasion and metastasis early in the disease process. There are several factors that actively drive melanoma progression including MET, a tyrosine kinase receptor overexpressed in melanoma and implicated in tumor growth, invasion and drug resistance.
Researchers utilized human cells in culture to determine if there were impactful changes on pro-cancer behavior in these cells with or without the drug YK-4-279 and found a significant reduction in growth and movement of the cancer cells when using it. In addition, experimental models treated with the drug had significantly delayed or no progression to aggressive disease.
According to the researchers these findings create the opportunity for YK-4-279 to be an option for melanoma treatments, either singularly or in combination with other available therapeutics. "We find that this molecule disrupts the interaction of two factors known to regulate melanocytes and promote melanoma through gene regulation. This work may impact other systems where these factors play a role, such as in the nervous system and in pigmentary disorders."
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These findings appear online in the journal Cancer Research.
Funding for this study was provided by grants from the National Institutes of Health, grant numbersR01CA184001, R01AR062547, T32GM007183, and 1UL1TR001430, the American Cancer Society, grant number RSG-CSM-121505, the Wendy Will Case Foundation, and the Friends of Dermatology-Chicago, the American Skin Association Daneen and Charles Stiefel Investigative Scientist Award, the Harry J. Lloyd Charitable Trust, the Falanga Scholar endowment (Boston University), Boston University Dermatology Scholars award, and the Department of Dermatology at Boston University.
Journal
Cancer Research