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Human melanoma is the deadliest form of skin cancer in the world, and its incidence is rapidly increasing every year 3-7% on average of the last decades, pointing to melanoma as one of the biggest health problem worldwide (Perlis & Herlyn, 2004). Recent statistics show that melanoma represents 1-3% of all malignant tumors, with Australia and New Zealand having the highest incidence (40 new cases/100 000 inhabitants per year), followed by North European countries and the USA; on the other hand, Japan and central Africa share the lowest incidence. Melanoma is one of the most aggressive tumors. Up to one-fifth of patients progress to metastatic (stage IV) disease, with a median survival of 6 months and a 5-year survival rate of less than 5% (Balch et al., 2001). Melanoma is resistant to conventional therapy such as chemotherapy, radiotherapy and immuno-therapy, as only 5-20% of the patients show a positive response to these treatments. To date, the only FDA-approved chemotherapy for melanoma is the alkylating agent dacarbazine (DTIC), which gives clinical responses in 5–10% of patients and cures in about 1%. The only other approved agents for disseminated melanoma are interleukin (IL)-2 and interferon (IFN)-a, which also have low response rates. During the radial phase, melanoma cells spread horizontally, while during the vertical phase they are able to invade the dermis and become able to generate metastasis (Garbe et al., 2011). Usually, the two phases represent the step-process that leads to aggressive melanomas: once melanoma has spread beyond its original location, it is usually highly resistant to therapies. There are four major types of melanoma: superficial melanoma, the most common type, flat and irregular in shape and colour, nodular melanoma, lentigo maligna melanoma, usually occuring in the elderly, and finally, acral lentiginous melanoma, the least common form of melanoma, which develops at high incidence in African Americans. Melanomas may develop in or near a previously existing precursor lesion or in healthy skin, and they can appear in the mouth, eye, or retina at the back of the eye, vagina, esophagus, anus, urinary tract, and small intestine. Age, sunburns during childhood, close relatives with a history of melanoma, presence of displastyc moles, weak immune-system, long-term exposure to sunlight and exposure to carcinogens are the most common risk factors for melanoma development. Melanoma originates from mutated melanocytes, which share with neurons a common neuroectodermal origin. Among the molecules that act as

Melanoma and the Nervous System – Novel Pathways Mediated by Neurotrophins and Their Receptors