Basal Cell Carcinoma and Its Treatment: Where Do We Go From Here?

Abstract

Basal cell carcinoma (BCC) is the most common cancer in the United States affecting millions of people annually. The pathophysiology of BCC is multifactorial and is influenced by environmental factors such as ultraviolet radiation exposure and genetics. There are common and aggressive subtypes of BCC, which are further characterized by their clinical appearance and histologic features. The common subtypes, such as nodular and superficial BCC are slow-growing and indolent. In contrast, the aggressive subtypes, such as the morpheaform and sclerotic variants are more likely to result in local tissue destruction, but rarely metastasize. The molecular pathogenesis of BCC was first discovered while studying basal cell nevus syndrome (BCNS), an inherited syndrome, which often manifests with large numbers of BCCs at a young age. BCNS researchers discovered the defective tumor suppressor gene, Patched 1, in the hedgehog signaling pathway that was found to underlie the pathophysiology of the syndrome as well as most sporadic BCCs. From further studies, additional members of the pathway have also been implicated as playing an oncogenic role in the formation of BCC. The gold standard treatment for non-advanced BCC is surgical excision. However, the focus of this review is the treatment of advanced BCCs, such as metastatic and locally advanced forms. Until recently, chemotherapy and radiation were the primary treatments for non-surgically resectable advanced BCCs. Now, with the recent advent of hedgehog pathway inhibitors, innovative treatment modalities for advanced BCC are at the forefront of current research. This thesis aims to conduct a thorough review of the epidemiology, clinical presentation, molecular pathophysiology, and current treatments of basal cell carcinoma with an emphasis on the role and limitations of hedgehog pathway inhibitors. Furthermore, the proposal of this thesis will reflect on the literature to hypothesize the future of advanced basal cell carcinoma treatment.