Experimental Models for BCC

Skin cancers are the most frequent human malignancies among Caucasians and the incidence is rising alarmingly due likely at least in part to increased exposure to ultraviolet-light (UV) as a consequence of decreasing ozone levels and increase in outdoor recreational activities. Skin tumors include malignant melanomas and non-melanoma skin cancers (NMSC) that are neoplasms of epithelial origin such as Basal Cell carcinoma (BCC) and Squamous Cell Carcinoma (SCC). Organ transplant recipients (OTR) have a 60to 100-fold higher risk for developing these tumors, and they behave significantly more aggressively than in immunocompetent patients [1]. BCCs infiltrate and destroy normal tissue but metastasize only rarely. Ultraviolet-light exposure, white skin, blue eyes, red hair, Celtic ancestry, and inability to tan have been identified as risk factors for BCC [2]. Sunlight, especially UVB (290–315 nm) radiation, is most effective in inducing BCCs. Current approved treatments include standard excisional surgery, Mohs micrographic surgery, radiation, cryosurgery, photodynamic therapy (PDT), local chemotherapy and application of immunomodulators such as imiquimod [3,4]. Following treatment, tumors have a 5year recurrence rate of 1-40% [3]. The highest overall cure rate for primary skin cancers is achieved by Mohs micrographic surgery but it may result in esthetic damage, especially in patients with aggressive histological BCC subtypes (e.g.morpheaform BCC) [3]. Although significant progress has been made in understanding the pathogenesis of NMSC, the host immune defense mechanisms that predict patient outcome are still largely unknown. Currently, most research on tumor immunosurveillance in NMSC has focused mainly on T-cell mediated, adaptive immune mechanisms. However, there is evidence that innate immune mechanisms are also important in NMSC [1]. Today it is well known that keratinocytes and other immune cells through various genes of the innate immune system such as toll-like receptors (TLRs) can also play a role in NMSC [1]. Since most of the tumors occur on the face, head and neck, patients will benefit from a more specific targeting of tumor cells with minimal damage to the healthy parts of the skin. A reliable experimental model is necessary to develop and evaluate new treatments.