Subtitles section Play video Print subtitles Moles, birthmarks, beauty marks. Most people have multiple moles, and they come in lots of different shapes and sizes. Usually they're harmless, but occasionally they could be a sign of a very serious disease: melanoma. So, when is a mole just a mole, and how does it turn into a deadly form of cancer? Now, not all melanomas start from a mole, but all moles are made up of the type of cells that can become melanomas: melanocytes. Hi, my name is Aaron Mangold. I'm an assistant professor of dermatology at the Mayo Clinic in Arizona. I specialize in cancer genomics as well as utilizing advanced forms of genetics to prognosticate cancers for spread to other areas of the body, as well as for therapeutic interventions. Melanocytes primarily protect skin cells from ultraviolet damage through the production of pigment called melanin. Melanocytes deliver melanin to the surrounding keratinocytes, or skin cells in the epidermis, giving our skin its color. When we come in contact with ultraviolet light from the sun, this melanin protects our skin from damage, while also signaling to the body to produce more melanin. This is why you might tan when you go out in the sun. And this system works pretty well, but it's not perfect. So melanocytes really have evolved over time to be extremely resistant to ultraviolet light. They've become extremely resistant to acquiring mutations that in normal cells might lead to apoptosis, or cell death. And they also are able to circulate innately throughout the body. Since melanocytes aren't as likely to die due to DNA damage from UV light, they obtain mutations and can continue to grow and may cluster together, forming non-cancerous growths called "nevi," or moles. Those damaged melanocytes can then acquire additional mutations and continue to proliferate forming a precancerous lesion or eventually a melanoma. One mutation that almost all moles have is in the gene BRAF, a protein that is part of cell signaling involved in cell growth. But, a single BRAF mutation is not enough to cause cancer. And not all melanomas even come from moles. So the way that melanoma, or the way that a melanocyte becomes a melanoma, occurs through a fairly long process. There's not one specific change that happens that leads to it. It's a series of changes. Additional mutations in genes can be caused by things like further damage due to UV light. These changes prevent natural cell death and lead to uncontrolled growth of the cancerous melanoma cells. Fortunately, melanomas can be removed if discovered early enough. And there are ways to check if a mole is irregular, which we'll talk about a little later. But, what happens if melanoma isn't caught? ...the melanoma cells, they're able to acquire certain properties that make them not want to stay in the skin any more. And once they acquire those, they can actually go into things called lymphatics in the bloodstream and then can spread. Once melanoma has reached this stage and has spread from the lymph nodes to other parts of the body, it's very hard to cure. It also has a high mortality rate, only 23% of patients survive past five years. So it's important to identify an abnormal mole soon so that it can be removed. Fortunately, there is an easy ABCDE rule to follow, which checks for asymmetry, irregular borders, uneven color, increasing diameter and an evolution or change in the mole. An individual might say that this lesion is just different. This doesn't look like everything else on me. That ugly duckling sign I think is also very useful in having some form of self body awareness and say, "I want this looked at." Specialists like Dr. Mangold are also starting to use immunotherapy to combat later stage melanoma, using the body's natural defenses to fight the disease. Normally our immune system will travel throughout the body, the immune cells will, and those immune cells will look at individual normal cells and say, "How abnormal are you?” ...And when they have those signals telling them that they've acquired too much damage, the immune system then kills them…. Well, cancer cells have figured out how to use certain proteins like that that will say, "Don't worry about it. Everything is okay. We're doing fine. Leave us alone." Recently, they figured out how to block those, how to block those signals that quiet the immune system. And it's really revolutionized not just the care of cancer as it pertains to melanoma, but cancer in general. But immunotherapy is still an emerging science. Doctors have to avoid making the immune system too active. This would result in an autoimmune disease, or an immune system that attacks healthy cells. It's really analogous to playing a musical instrument or playing a piano. You have all the keys that are there. Yet, you can make good music, or you can make bad music. And we're trying to figure out now, how do we make good music and how do we avoid that kind of bad music? While immunotherapy is still developing, there is one treatment that everyone can take part in. You don't want people to lose sight of what's important, and I think it was Bert Vogelstein who said this, that if you could give someone a pill and tell them, "This pill that I give you is going to reduce your risk of cancer by 50%," that it would be across every news organization, every magazine cover. Someone would get a Nobel Prize for it. And we do have that pill. That pill is primary prevention through healthy behaviors, healthy eating, different things that we can do as individuals that will reduce those risks.