Melanoma is the most dangerous form of skin cancer. As with all skin cancer, melanoma develops due to genetic mutations of the DNA (either by inheritance or UV radiation). Risk factors for the development of melanoma include: skin pigmentation (fair-skinned individuals are at a higher risk), childhood exposure to sunlight, number of peeling/blistering sunburns in a lifetime, a family history of melanoma, and those born with multiple atypical/dysplastic moles, as well as those with large moles at birth. Interestingly, socio-economic status seems to play a large role in melanoma development, with the highest rates occurring in professionals. Melanomas are most commonly found on the back in men and on the legs in women, both areas that are more frequently exposed to the sun.
Due to the vast advancements in cancer therapy, melanoma, as well as many other cancers, is not particularly a death sentence anymore. As with most cancers, melanoma has many treatment options depending on what stage in the game the cancer is diagnosed. For uncomplicated melanomas that have not spread to the lower layers of the skin, or metastasized to the lungs or brain, surgical removal with wide margins is recommended, followed by either nothing (if the melanoma was caught early enough) or the biopsy of a nearby lymph node (though controversial, this intervention may be useful in determining if the melanoma started metastasizing or not). Unfortunately, surgical resection of melanoma is not always successful and may result in recurrence in up to 50% of all cases. Melanomas that are classified as “high-risk” may require further management such as year-long interferon treatment, immune-enhancement (Aldara), chemotherapy (DTIC, Temodar), radiation therapy, or immunotherapy (a whole slew of new drugs).
Immunotherapy is a branch of treatment options that treats diseases (or cancer, in this case) by augmenting or suppressing the normal human immune response. By manipulating the immune system, it is possible to direct the human body to either “fight” the disease (as with cancer, such as melanoma), or stop “attacking” itself (as with autoimmune disorders, such as rheumatoid arthritis). New immunotherapeutics include Proleukin, which was the first new therapy approved for melanoma treatment in 20 years (until recently). Proleukin is really interleukin-2, a normally occurring human immune system modulator that activates white blood cells to attack the melanoma cancer cells. Another immunotherapeutic is Yervoy, a human antibody that binds to receptors on the surface of white blood cells causing them to activate and constantly destroy tumor cells.
Earlier this year, the FDA announced that they had approved two new drugs for melanomas that could not be surgically removed – Tafinlar and Mekinist. Both medications are immunotherapeutics and target BRAF-positive melanomas specifically, (previous BRAF-targeted treatments include Zelboraf). BRAF is a gene that is mutated in about 60% of melanomas and is correlated with a particularly aggressive, unrespectable form of melanoma. New studies are being conducted to improve the action of both of these drugs by combining them, and so far the results seem successful.
The newest areas of research regarding melanoma therapy involve adoptive cell therapy or gene therapy. For instance, the NIH is working on a system in which white blood cells found in a patient’s own melanoma may be isolated, grown in the lab, and be reintroduced to the patient, thus creating a subset of white blood cells in the patient’s body that are tumor fighting machines. Another option may be the use of Sutent (FDA approved for renal cell carcinoma and gastrointestinal tumors), which targets receptors in the body to train the immune system to fight cancer cells. Though not as successful as some of the other drugs mentioned previously, this treatment choice may be good for late-stage, metastatic melanoma.
With the advances medical science has been making in all fields of cancer therapeutics, it is impressive the amount of the work that has gone into developing novel treatment possibilities for melanoma. However, the most important concept in melanoma treatment is early detection (with prevention obviously being “up there” as well). By detecting a melanoma early, a patient and doctor reduce the chance of having to face further treatment as surgical resection may just do the trick. So everyone remember their sunscreen and their ABCDEs (asymmetry, border irregularity, colour changes, diameter and enlargement/evolving) as these are the most important principles in combating all skin cancers, including melanoma.
Margit Lai Wun Juhasz
Mount Sinai Medical Student