Topical Vitamin D3, Diclofenac or a Combination of Both to Treat Basal Cell Carcinoma

Basal cell carcinoma (BCC) is the most frequent malignant tumor in Caucasians and the incidence is still increasing with 3-8% each year. Since BCCs generally occur on sun-exposed areas of the skin, the rice in incidence is mainly explained by the increasing exposure to (intermittent) ultraviolet radiation. Surgical excision is still the standard treatment for (micro)nodular BCCs. The costs as well as the increased workload are stressing the health care system even further and posing BCC an important health care problem. Since half of the BCCs arise primarily on the face \& (bald) head and treatment by surgical excision may result in disfiguring scars, patients often experience a dramatic decrease of their quality of life. Hence, there is an urgent medical and societal need for a simple and cheap (targeted) treatment, preferably to be performed by the patients themselves. This treatment must be safe and effective. Such treatment is not available yet. BCC tumorigenesis is complex and must be multifactorial. Genetic alterations of multiple components of the Sonic Hedgehog (SHH) pathway are involved in sporadic BCC pathogenesis; inactivating mutations in Patched-1 (PTCH1) and activating mutations of Smoothened (SMO) and Suppressor of Fused (SU(FU)). With this knowledge, inhibition of the SHH pathway by SMO antagonists was successfully administered, however treatment resulted only in partial clinical response ofBCC. Recently, involvement of the Wingless (Wnt) pathway has been proven to be essential in BCC tumorigenic response. Moreover, a recent study of our own department provides the first evidence that epigenetic alterations, particularly promoter hypermethylation, influence both the SHH and Wnt pathway (own data, not published), which can serve as therapeutic targets. Both non-steroidal anti-inflammatory drugs (NSAlDS) and vitamin D derivatives are able to directly or indirectly target the Wnt pathway. Furthermore, vitamin D3 is able to inhibit Smoothened (SMO) in vitro, resulting in inhibition of the SHH pathway. Although in vivo studies are lacking, the investigators assume that topical application of these drugs may inhibit BCC growth and/or may cure BCC and thus might provide very promising future perspectives. Calcitriol and NSAlDs ointments are both already available for other indications and save in use. Eventually, our approach may result in a systematic approach to BCC, targeting (epi)genetic changes to treat and/or prevent further tumour growth.