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Skin health and protection are important topics of which to stay mindful as we approach the eagerly awaited sun-filled days of summer. It is also an opportune time to take a look at emerging treatments for a prevalent type of skin cancer: melanoma. Most often, melanoma is caused by ultraviolet radiation from the sun or tanning beds. If the melanoma is caught early, it is almost always curable with only a 2% risk of death. However, if it advances and metastasizes to other parts of the body, it is extremely hard to treat and may be fatal. Of all types of skin cancer, it causes the most deaths. An estimated 10,130 people in the US die annually from melanoma.
Aside from surgical resection, there are a variety of drug therapies on the market for melanoma. These include immunotherapy, targeted therapy, BRAF and MEK inhibitors, immune checkpoint blockade therapies, chemotherapy, and radiation therapy. In a study utilizing an experimental model of melanoma lung metastasis, inhibition of the myocardin-related transcription factor (MRTF) pathway reduced both the size and number of lung metastases, supporting the target of MRTF transcriptional pathway as a potential approach to treating melanoma.
Now a promising novel compound in the pipeline has produced noteworthy results, particularly related to melanoma metastasis. This new treatment is a combination of an existing chemical compound and investigational drug. It was found to reduce melanoma metastasis by approximately 90%. This human-made, small molecule drug attacks the gene’s ability to produce RNA molecules and certain proteins in melanoma tumors, shutting down the transcription process that allows the cancer to spread. Investigators demonstrated how compounds could stop proteins, the MRTFs, from initiating the transcription process in melanoma cells. Ras homology C (RhoC), which is a protein found in the signaling pathway that allows the disease to spread, turns on the MRTFs. The compound successfully reduced the spread of melanoma cells by 85% to 95%.
This discovery is significant in melanoma drug development. The findings suggest that the MRTF signaling protein is a potential new target for drug therapy. Additionally, the study particularly looked at melanoma metastases. This endpoint is highly clinically significant, given that melanoma becomes fatal after progression and metastasis but is very treatable if caught early. The next step is to identify which patients have the RhoC pathway turned on to determine which patients are best candidates for this type of treatment. There is a significant unmet need in the drug market for patients with advanced disease. Continued efforts to optimize MRTF transcription inhibitors are needed, particularly enhancing potency, reducing acute toxicity, and improving bioavailability and pharmacokinetics. New compounds are crucial, and this discovery may save lives.
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Haak AJ, Appleton KM, Lisabeth EM, et al. Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma. Molecular Cancer Therapeutics. 2017;16(1):193-204. doi:10.1158/1535-7163.MCT-16-0482.
Melanoma. Skin Cancer Foundation website. http://www.skincancer.org/skin-cancer-information/melanoma. Accessed June 15, 2018.