Pharmacotherapeutics targeting the hedgehog pathway: emerging treatments for metastatic basal cell carcinoma
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Basal Cell Carcinoma (BCC) is one of the most commonly diagnosed nonmelanoma skin cancers (NMSC) in the world. While BCC is usually readily treatable with surgical excision of the tumor, its metastatic form (mBCC) is far deadlier, with an average patient survival of eight months following diagnosis. A majority of mBCC cases is tied to mutations causing dysfunction in the Hedgehog Pathway (HHP), a pathway that induces basal cells in the skin to divide rapidly and repeatedly. For this reason, there has been an emphasis over the last thirty years on developing novel drug-based therapeutics for the treatment of mBCC that specifically target the HHP. This paper will examine the body of published research investigating current and developing mBCC treatments, with a focus on the therapeutic modalities of the two current treatments for mBCC, Vismodegib and Sonidegib, and one potential treatment currently under investigation, Itraconazole/ATO. A review of the clinical research will detail the mechanism of action for each drug with regard to the HHP and its components, the efficacy of the treatment, and adverse effects seen in patients during treatment.