Posted June 29, 2022

According to the Centers for Disease Control (CDC), more than 90% of melanoma in the United States (U.S.) is due to ultraviolet (UV) exposure.¹ The American Cancer Society advises people that the most important way to decrease their melanoma risk is to avoid UV exposure through the use of protective clothing and sunscreen and by avoiding tanning beds.² Despite these prevention strategies, the rates of melanoma have been rising rapidly over the past few decades, with an estimated 99,780 new cases diagnosed in 2022.³ Melanoma cases are also increasing in active duty Service Members, who spend prolonged periods of time outside during their deployments to areas of high UV radiation.⁴ Given this information, the U.S. Congress established the Melanoma Research Program (MRP) in Fiscal Year 2019 (FY19) to fund research of exceptional merit in the field of melanoma. Since its inception, MRP has issued a Challenge to the research community to redefine prevention to include improved detection and monitoring capabilities, as well as inhibiting the initiation of melanoma, the emergence from tumor dormancy, and the development of metastases. Below are a few examples of how MRP funded investigators are responding to the MRP Challenge Statement.

Understanding Transition from Nevi to Melanoma Occurring Within the Skin Epidermis
Mayumi Ito, Ph.D., New York University School of Medicine
Mid-Career Accelerator Award

In order to understand how to prevent melanoma, it is important to first understand how melanoma develops. Melanomas typically arise from melanocytes in the epidermis, the outermost layer of skin. One limitation of using model systems is that mice have many melanocytes in the dermis (unlike humans), meaning that the melanomagenesis process in mice is likely different from humans. Dr. Ito and others have recently developed a mouse model (called c-kit creER) in which melanomas first develop in the epidermis without simultaneous melanoma expansion in the dermis.⁵ Now, with a FY20 Mid-Career Accelerator Award, Dr. Ito and her team will use this novel mouse melanoma model to map the transition of nevi to melanoma in order to identify novel biomarkers and mechanisms for melanomagenesis. They will also use their novel mouse model to investigate whether immunotherapy can prevent the benign nevi to melanoma transition. Dr. Ito expects that this project will identify novel characteristics that can be used to predict melanomagenesis risk and identify new therapies to prevent the formation of melanoma.

Link:
Public and Technical Abstracts: Understanding Transition from Nevi to Melanoma Occurring Within the Skin Epidermis

Engineering Skin Microbiome to Generate Natural Sunscreens for Prevention of Melanoma
Nalinikanth Kotagiri, Ph.D., University of Cincinnati
Idea Award

Sunscreen is considered one of the most effective ways to prevent skin cancer. However, there are several drawbacks: effectiveness is dependent on topical application and reapplication about every 2 hours, and some ingredients are damaging to aquatic environments.⁶ Therefore, there is a need for long-lasting, biodegradable alternatives to the sunscreens currently on the market. This project will engineer a novel photoresponsive, probiotic sunscreen platform using non-pathogenic Staphylococcus epidermidis to synthesize mycosporine-like amino acids which have superior sunlight filtering properties and are naturally produced in marine cyanobacteria. Dr. Kotagiri envisions that this product could be applied to provide both short-term and long-term protection as these bacteria would serve as “living skin-protective factories” on the skin surface, constantly generating UV-protecting compounds. The successful completion of this project will be the first step toward creating a novel probiotic product that synthesizes and releases sunscreen directly on the skin to prevent melanomagenesis.

Link:
Public and Technical Abstracts: Engineering Skin Microbiome to Generate Natural Sunscreens for Prevention of Melanoma

Preventing Metastasis of High-Risk Melanoma
Wesley Yu, M.D., Oregon Health and Sciences University - Portland
Idea Award

The vast majority of melanomas (83%) are diagnosed at an early, localized stage. However, approximately 10-15% of these localized melanomas will eventually metastasize, despite appropriate local treatment.⁷ The time between early diagnosis and metastasis presents an important opportunity to halt the metastatic process and decrease mortality. Genetic tests recently developed by Gerami, et al.⁸ can be used to identify melanomas that are at high risk for future metastasis. However, there are currently no drugs that can be taken on a long-term basis to prevent metastasis of melanomas identified by these tests. In preliminary studies, Dr. Yu conducted a drug screen that identified statins as a potential class of drugs that could reverse the “high-risk” gene expression profile associated with melanoma metastasis. Statins are extremely well-suited for use as a long-term preventative medication since they are already used to treat high cholesterol and have a very tolerable side effect profile. With his FY20 Idea Award, Dr. Yu is redefining the concept of melanoma prevention by studying the use of statins to prevent metastasis of genetically high-risk melanomas. Dr. Yu worked with the U.S. Department of Veterans Affairs (VA) Informatics and Computing Infrastructure (VINCI) to obtain clinical data on melanoma patients through the VA Corporate Data Warehouse (CDW). Analysis of this data, which was recently published, suggest an association between statin use and improved overall survival for Veterans with melanoma.⁹ Dr. Yu will continue his investigation using animal models of melanoma to evaluate the effects of statins on immune responses and melanoma metastasis via the lymph nodes. Since statins have U.S. Food and Drug Administration approval and are inexpensive, their use to prevent melanoma metastasis could have immediate lifesaving impact.

Link:
Public and Technical Abstracts: Preventing Metastasis of High-Risk Melanoma

References:

¹https://www.cdc.gov/vitalsigns/melanoma/index.html

²https://www.cancer.org/cancer/melanoma-skin-cancer/causes-risks-prevention/prevention.html

³https://www.cancer.org/cancer/melanoma-skin-cancer/about/key-statistics.html

⁴Riemenshneider MD, Liu J, and Powers GJ. 2018. Skin cancer in the military: A systematic review of melanoma and nonmelanoma skin cancer incidence, prevention, and screening among active duty and veteran personnel. J Am Acad Dermatol 78(6):1185-1192.

⁵Sun Q, Lee W, Mohri Y, et al. 2019. A novel melanoma mouse model demonstrates that oncogenic melanocyte stem cells engender melanoma resembling human disease. Nat Commun 10(1):5023. https://pubmed.ncbi.nlm.nih.gov/31685822/

⁶https://oceanservice.noaa.gov/news/sunscreen-corals.html

⁷https://seer.cancer.gov/statfacts/html/melan.html

⁸Gerami P, Cook RW, Wilkinson J, et al. 2015. Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res 21(1):175-173. doi:10.1158/1078-0432.CCR-13-3316

⁹Madison CJ, Heinrich MC, Thompson RF, Yu WY. 2022. Statin use is associated with improved overall survival in patients with melanoma. Melanoma Res. doi: 10.1097/CMR.0000000000000822. Epub ahead of print.