Skin Cancers

Skin cancers (i.e., basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma belong to the most frequent tumors. Their formation is based on constitutional and/or inherited factors usually combined with envirnomental facts, mainly UV-irradiation through long term sun exposure. UV light can randomly induce DNA damage in keratinocytes, but it can also mutate genes essential for control and surviellance in the skin epidermis. Various repair mechanisms exist. For example, DNA damaged cells are eliminated by apoptosis (sunburn cells). This occurs under the control of the p53 suppressor gene. Fas-ligand (FasL), a member of the tumor necrosis superfamily, which is preferentially expressed in the basal layer of the skin epidermis, is a key surveillance molecule involved in the elimination of sunburn cells. However, UV light exposure downregulates FasL expression in keratinocytes and melanocytes leading to the loss of its sensor function. Moreover, important control genes can also be direclty affected by UV light. Mutation in the p53 gene is the starting point for the formation of SCC and some forms of BCC. Other BCCs originate through UV light mediated mutations of genes of the hedgehog signaling pathway which are essential for the maintainance of cell growth and differentiation. Once the keratinocytes or melanocytes have been transformed they reexpress FasL which may allow the expanding tumor to evade the attack of immuen effector cells.

Melanoma Treatments: The most recent FDA approved drug for melanoma is ipilimumab from Bristol-Myers Squibb Co. The drug has been shown to work in a small segment of the population and provided 4 months more time of life expectancy compared to older approved FDA drugs. The drug works by blocking a molecule called CTLA-4 which interfers with the protective activity of white blood cells.