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    Moving toward personalized medicine for melanoma

    Dermatologists have long known that the majority of melanomas arising from the skin  are associated with exposure to ultraviolet light, but a presentation at the summer meeting of the American Academy of Dermatology (August 2015, New York) allowed clinicians to deepen their knowledge, and provided a framework on the current understanding of the disease.

    READ: Skin cancer screenings target marathoners

    “We have long known that cutaneous melanoma is different from other forms, such as those that arise from the acral sites, uveal tract or the mucous membranes. One study found 171 mutations per sun-exposed tumor, compared with nine mutations per sun-shielded tumor,” says Julide Tok Celebi, M.D., professor in the departments of dermatology and pathology at the Icahn School of Medicine, Mount Sinai, New York.

    Scientists have recently learned that cutaneous melanoma has the highest mutational load among all cancers.

    “With prostate cancer, we find 10 or 12 mutations per megabase,” she says. “Childhood cancers such as acute myeloid leukemia harbor a very low mutational burden. Melanoma is the highest with 100 to 120 mutations per megabase.”

    Lung cancer carries the second-highest mutational burden. It’s important to note that melanoma and lung carcinoma are both associated with environmental carcinogens (ultraviolet radiation and smoking, respectively), which implicates significant DNA damage, Dr. Celebi says.

    ALSO READ: Protein p15 may influence melanoma progression

     “We’ve learned over the past few years through advances in next generation sequencing that mutational load in cutaneous melanoma correlates with sun-exposure signatures at the molecular level,” Dr. Celebi says.

    The knowledge has clinical significance, too. “Researchers found that melanomas with more than 100 mutations did better with an anti-CTLA4  monoclonal antibody,” an immunotherapy which has become clinically available since 2011, she adds.[1]

     “We are hoping that we are getting closer to personalized medicine in melanoma. Immunotherapy works and can be durable. Patients with stage-4 disease are not relapsing right away. We have patients that are surviving three, four, or five years beyond diagnosis, but not everyone, and a subset of patients are not responding at all. Ten years ago, five-year survival was 15%, and now some patients are living more than five years with no disease. We never had such an exciting momentum in the treatment of metastatic melanoma before,” notes Celebi.

    NEXT: New classification schemes and molecular tests

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