Basal cell carcinoma (BCC) is a subtype of nonmelanoma skin cancer (NMSC), with an increasing incidence worldwide. Currently, excision of the tumour with histological control is the standard therapy. However, high incidence rates have led to concern about the economic burden imposed by BCC management in many countries. Imiquimod is a member of a novel class of immune response modifiers (IRM), which works by using the toll-like receptor (TLR)-7. Although the exact mode of action is so far unknown, it is suggested to induce the expression of different cytokines like interleukin (IL)-1, IL-6, IL-12, interferon (IFN)-alpha and tumour necrosis factor (TNF)-alpha, which stimulate or enhance both the innate immune system and the cell-mediated immune response. Pre-clinical studies have indicated the potential of this TLR-7 agonist for the treatment of precancers and tumours in humans. A number of Phase II trials have demonstrated the efficacy of imiquimod for the treatment of BCC, although the most appropriate dosing regimen is being confirmed in Phase III studies. Imiquimod 5% cream for the treatment of mainly superficial BCC appears to be an effective and well-tolerated treatment option.
Multiple international studies assess risk factors and pathophysiology of skin cancer in organ transplant patients, with variable results in the literature. Large multicenter studies with thorough multivariant analysis may provide useful information for center-independent analysis of pathogenesis factors for transplant-related skin cancer.
Toll-like receptor (TLR)-7 agonists represent a new group of immune response modifiers, which include imiquimod and resiquimod (R-848). Topically applied imiquimod is used for the treatment of both external and perianal genital warts, and benign and malignant epithelial lesions. Based on the induction of interferons and other cytokines in vitro and in vivo, regression of epithelial lesions probably depends on induction of both innate and cellular immune responses. As clinical remission is not always associated with inflammation, other mechanisms may also be involved. Using two different assays for detection of apoptosis (TUNEL test and gel analysis of DNA fragmentation), we observed induction of apoptosis by imiquimod in human epithelial cell lines (HeLa S3) and keratinocytes (HaCaT, A431 cells), as well as in mouse fibroblasts (McCoy cells). These findings suggest that the mode of action of imiquimod to eliminate virus-infected, dysplastic or neoplastic epithelial cells may also include the induction of apoptotic processes.
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