MedicalResearch.com Interview with: John D'Orazio, M.D., Ph.D. Drury Pediatric Research Endowed Chair Associate Professor, Univ. KY College of Medicine Pediatric Hematology-Oncology The Markey Cancer Center Lexington, KY 40536-0096 Medical Research: What is the background for this study? Dr. D'Orazio: Malignant melanoma is the deadliest of skin cancers, and it’s incidence has increased enormously over the last several decades.  In the 1930’s only one in every fifteen hundred Americans would get melanoma in his/her lifetime.  Now it’s one in fifty or sixty.  Plus, it often affects young adults in the prime of their lives.  Altogether, nearly 10,000 Americans die of melanoma every year.  However, risk is not equally shared.  Fair-skinned people who tend to burn rather than tan from sun exposure have a much higher risk than dark skinned people.  On the surface, it would appear that the amount of melanin in the skin would be the only determinant of melanoma risk but the truth is more complex.  Our lab has been interested in a particular hormonal pathway in the skin that directly influences melanoma risk.  When UV radiation (sunlight) hits the skin, it causes damage to the cells of the skin.  Cells respond to this damage to protect themselves against further injury.  One way in which they do this is by turning on a hormone called melanocyte stimulating hormone, abbreviated “MSH”.  Made by keratinocytes, the most abundant cells in the epidermis, MSH is directly responsible for ramping up melanin production by melanocytes, the cells that make the pigment in the skin that gives us a tan.  This pigment called melanin acts as natural sunscreen and blocks UV radiation from penetrating into the skin.  This is very important because people who can tan are in a much safer state the next time they get sun exposure.  Because they have more melanin in the skin, the UV won’t cause as much damage.  The key is to realize that UV causes mutations in melanocytes, and with enough damage to the DNA, melanocytes can turn cancerous and become melanomas.   People who have the melanoma-prone, “can’t tan” skin type often have problems in this MSH hormonal pathway.  Specifically, they have inherited problems with the receptor on melanocytes that binds to MSH and makes the cells make more pigment.  This protein, called the melanocortin 1 receptor (or “MC1R”), is the way that melanocytes sense that the skin has been injured and needs more melanin.  If the MC1R won’t signal, then melanocytes just sit there and can’t be induced to make more melanin pigment.  Surely this is a major reason why people with MC1R signaling defects are at high risk of melanomas. (more…)