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MRF Funding Advances Mucosal Melanoma Research

Guest blog post by Florian Karreth, PhD, a 2018 Career Development Award recipient from Moffitt Cancer Center:

In 2018, my laboratory at the Moffitt Cancer Center received funding from the Melanoma Research Foundation (MRF) to study mucosal melanoma. We typically think of melanoma as a cancer of the skin. However, melanomas can form on other parts of the body. Mucosal melanoma is a rare type of melanoma – representing only 2% of all melanoma cases – that develops on the mucous membranes of the mouth, nose, anus and vagina. Only about 25% of patients diagnosed with mucosal melanoma survive for five years, making mucosal melanoma far more deadly than melanoma of the skin. On the one hand, this poor survival rate can be attributed to mucosal melanoma typically being diagnosed at more advanced stages. On the other, research over the past decade has shown that mucosal melanoma is a distinct biological and clinical entity. Given their anatomic locations, ultraviolet radiation plays no part in causing mucosal melanoma. Moreover, mutations in genes that are known to cause or promote melanoma of the skin are only very rarely found in mucosal melanoma. Instead, abnormalities affecting the chromosomes are much more common. This also means that therapies used to treat patients with melanoma of the skin perform very poorly when used for patients with mucosal melanoma. We therefore need to better understand the genetic and biological changes contributing to mucosal melanoma development to design better treatments.

We often use the laboratory mouse to study cancer biology and therapy. To do so, we introduce the genetic changes found in human cancer into the DNA of the mouse. The goal is to generate mouse models that very closely mimic the genetics and biology of the corresponding human cancer, which maximizes the information that can be obtained from these models. While mouse models are invaluable research tools, their downside is that they are slow and expensive. My lab has pioneered an approach allowing us to quickly develop new mouse models to study melanoma of the skin. The funding from the MRF supported our work to adapt this approach for mucosal melanoma. We started by developing mouse models having a mutant version of the cKIT gene, which is often found overactive and mutated in human mucosal melanoma. We have three primary goals. First, to create the first mouse model of human mucosal melanoma. Second, to confirm that mutant cKIT plays a critical role in mucosal melanoma development. And third, to use this new mouse model to test drug treatments against mucosal melanoma that carries the mutant cKIT gene. Our preliminary results are very promising, and we will continue to use and refine our mucosal melanoma mouse models. We believe that these models will become a useful resource for the mucosal melanoma research community.

Funding from the MRF had a much bigger impact than just allowing us to develop mucosal melanoma mouse models. Our work sparked an initiative of our cutaneous melanoma group at Moffitt Cancer Center to conduct research into other types of rare melanoma, such as acral melanoma (melanoma of the hands and feet) and pediatric melanoma in children and adolescents. This initiative brings together Moffitt researchers with complementary areas of expertise: we work closely with Drs. Sondak (Surgery), Messina and Tsai (Pathology), Smalley and Premi (Tumor biology), Adeegbe (Immunology), Koomen (Proteomics) and Chen and Teer (Bioinformatics/Biostatistics) to better characterize these understudied types of melanoma. Additionally, multiple doctoral and post-doctoral trainees are involved in these studies, and we are proud to train the next generation of melanoma researchers. It takes a village, and our combined efforts will ultimately lead to the development of therapies to treat patients with mucosal and other types of rare melanoma.

The MRF is proud to support research leading to improved treatments for all forms of melanoma and, one day, a cure. Your support makes this possible; please consider a tax-deductible gift today: