Basal Cell Carcinoma and the Carcinogenic Role of Aberrant Hedgehog Signaling

Anna Saran

Disclosures

Future Oncol. 2010;6(6):1003-1014. 

In This Article

Abstract and Introduction

Abstract

Basal cell carcinoma (BCC) is the most frequent cancer in the white population and its incidence appears to be increasing worldwide. While the majority of BCCs arise sporadically, many cases are attributable to basal cell nevus syndrome, or Gorlin syndrome, an autosomal dominantly inherited disorder characterized by the occurrence of multiple BCCs and by extracutaneous tumors. Genetic studies on patients with basal cell nevus syndrome indicate deregulation of the Hedgehog (Hh) pathway in epidermal keratinocytes as the primary event in the pathogenesis of BCC. This article summarizes the recent progress in understanding Hh-dependent BCC tumorigenesis, as well as evidence for deregulation of other molecular pathways, primarily the Wnt developmental pathway. Understanding the molecular genetics of BCC development has provided new opportunities for molecular therapy of this cancer by targeting Hh and other signaling pathways.

Introduction

Basal cell carcinoma (BCC) is the most common skin cancer, accounting for approximately 70% of all skin malignancies. The principal etiologic factors in human BCC include UV and ionizing radiation, chemical carcinogens and possibly infection with human papillomaviruses.[1] Arsenic ingestion through drinking water has also been associated with increased risk of BCC.[2] The incidence of metastatic events in BCC is exceedingly low. Infrequently, however, the clinical course may be aggressive (<0.1% of cases), and metastases can develop regionally (e.g., lymph nodes) or at sites distant from the primary tumor,[3,4] generally in the lung and less commonly in bone and internal organs.[5–7] In addition, BCCs tend to be locally aggressive and 5–9% may have multiple recurrences,[8] causing significant tissue destruction by local invasion. In the last decade, substantial progress has been achieved in our knowledge of the molecular pathogenesis of BCC. This article reviews some of the recent advances in this field and how they can contribute to the treatment of this very common human tumor.

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