Disease Description

Melanoma is considered the most dangerous form of skin cancer. These cancerous growths develop when unrepaired DNA damage to skin cells (most often caused by ultraviolet radiation from sunshine or tanning beds) triggers mutations (genetic defects) that lead the skin cells to multiply rapidly and form malignant tumors. These tumors originate in cells called melanocytes. Melanocytes are the cells responsible for giving our skin their color. Melanomas often resemble moles; some develop from moles. The majority of melanomas are black or brown, but they can also be skin-colored, pink, red, purple, blue or white. Melanoma is caused mainly by intense, occasional UV light exposure (frequently leading to sunburn), especially in those who are genetically predisposed to the disease. [1]

Prevelance

Melanoma is the fifth most common cancer in men and seventh in women in the United States. The number of melanoma cases is increasing faster than for any other type of cancer. Estimates for 2014 are that 76,100 invasive melanomas will be diagnosed in the United States and that melanoma could claim 9710 lives [2].

Current Treatment Options

At present, prevention and early detection are the only effective measures against melanoma. Melanoma basically remains a surgical disease, and excision of thin, biologically early tumors offers the best chance of cure. Despite intensive research, no effective therapies exist for advanced melanoma. Only high-dose IFN -2b has a reproducible benefit in stage II and III patients, but owing to its numerous side effects, modest efficacy, and high cost, it is not used worldwide and is inconsistently used in the United States. For patients with stage IV melanoma, randomized, controlled trials have shown no significant advantage of any specific drug or combination of drugs. Dacarbazine, the only cytotoxic drug approved by the FDA for the treatment of metastatic melanoma, remains the benchmark, but it produces responses of moderate duration and only in a small fraction of the patients. New therapeutic strategies are therefore necessary for the management of melanomas.[3]

Evidence for and the Proposed Mechanism of Cannabinoid Therapeutics

Accumulating recent evidence implicates the endocannabinoid system in the regulation of growth of skin cells. Cannabinoids were also reported to inhibit the growth of melanomas that express cannabinoid receptors (CB1 and CB2) by decreasing growth, proliferation, blood vessel growth and metastasis formation, while increasing cell death. [4]

Groups have studied the potential efficacy of cannabinoids as antitumoral agents against melanoma and showed that these compounds exert a remarkable growth-inhibiting effect on melanoma cells that is evident under various experimental settings (animals with different immune statuses, melanoma cells inoculated at different sites, cannabinoids injected by different routes). Moreover, this is associated with an improvement of various tumor-progression parameters (decreased proliferation and vascularization, increased cell death), as well as with an inhibition of tumor-cell metastatic spreading, one of the clinical hallmarks of advanced melanoma.[5]

Together with the implication of cannabinoid receptors (CB2) in the control of processes such as pain initiation, emesis, and inflammation, opens the attractive possibility of finding cannabinoid-based therapeutic strategies devoid of nondesired psychotropic side effects. Specifically, the antiproliferative effect of cannabinoids reported may set the basis for a new therapeutic approach for the treatment of malignant melanoma.[5]

1. Skin Cancer Foundation. www.skincancer.org/

2. National Cancer Institute. http://seer.cancer.gov/statfacts/html/melan.html

3. Blazquez, C. et al. (2006) Cannabinoid receptors as novel targets for the treatment of melanoma. FASEB J. 20, 2633–2635

4. Pacher, P. et al. The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends Pharmacol Sci. Aug 2009; 30(8): 411–420.

5.Blazquez, C. et al. (2006) Cannabinoid receptors as novel targets for the treatment of melanoma. FASEB J. 20, 2633–2635