Abstract
Simple SummaryBasal cell carcinoma is the most common human cancer worldwide. The molecular basis of BCC involves an interplay of inherited genetic susceptibility and somatic mutations, commonly induced by exposure to UV radiation. In this review, we outline the currently known germline and somatic mutations implicated in the pathogenesis of BCC with particular attention paid toward affected molecular pathways. We also discuss polymorphisms and associated phenotypic traits in addition to active areas of BCC research. We finally provide a brief overview of existing non-surgical treatments and emerging targeted therapeutics for BCC such as Hedgehog pathway inhibitors, immune modulators, and histone deacetylase inhibitors. Basal cell carcinoma (BCC) is a significant public health concern, with more than 3 million cases occurring each year in the United States, and with an increasing incidence. The molecular basis of BCC is complex, involving an interplay of inherited genetic susceptibility, including single nucleotide polymorphisms and genetic syndromes, and sporadic somatic mutations, often induced by carcinogenic exposure to UV radiation. This review outlines the currently known germline and somatic mutations implicated in the pathogenesis of BCC, including the key molecular pathways affected by these mutations, which drive oncogenesis. With advances in next generation sequencing and our understanding of the molecular genetics of BCC, established and emerging targeted therapeutics are offering new avenues for the non-surgical treatment of BCC. These agents, including Hedgehog pathway inhibitors, immune modulators, and histone deacetylase inhibitors, will also be discussed.
Highlights
Of all human cancers, basal cell carcinoma (BCC) is the most common worldwide, and in many countries, its incidence continues to increase, representing a significant public health burden [1]
This review will discuss in more depth the currently known germline and somatic mutations implicated in the pathogenesis of BCC, as well as the underlying molecular pathways affected
While germline polymorphisms result in an inherited predisposition to BCC, subsequent sporadic somatic mutations are required before cancer develops
Summary
Basal cell carcinoma (BCC) is the most common worldwide, and in many countries, its incidence continues to increase, representing a significant public health burden [1]. The molecular pathogenesis of BCC is complex, and involves an interplay of inherited genetic susceptibility [6] and sporadic somatic mutations [7]. The former predisposes an individual towards the development of BCC, and can include single nucleotide polymorphisms (SNPs), inherited disorders, and genetic traits [6], but the latter is generally required to induce carcinogenesis. We will give an overview of established and emerging targeted, non-surgical, therapeutics which could revolutionize the treatment of this common and important skin cancer
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