Abstract

Cutaneous basal cell carcinoma (BCC) is the most common type of human tumor, and its incidence rate is increasing worldwide. Up until a few years ago, therapeutic options have been limited for patients with advanced BCC (including metastatic and locally-advanced BCC). Over the last few years, promising systemic therapies have been investigated for the treatment of advanced BCC. In particular, the Hedgehog signaling inhibition has shown remarkable results for this population. Hedgehog inhibitors, represented by vismodegib and sonidegib, have been approved by the Food and Drug Administration and the European Medicines Agency for the treatment of both locally advanced and metastatic BCC, with, generally, a good safety profile. Notwithstanding the late onset of BCC in the global population, associated with life expectancy increase, only a few clinical trials have evaluated the efficacy and safety profile of Hedgehog inhibitors in this complex and neglected population. Herein, we review the major mechanisms implicated in the pathogenesis of BCC focusing on the Hedgehog signaling pathway and its therapeutic role in the elderly population. Finally, we report two case reports of BCC elderly patients in order to demonstrate both efficacy and safety of the Hedgehog inhibitors.

Highlights

  • Non-melanoma skin cancers (NMSCs) include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), representing the most common cancers in the Caucasian population [1].BCC, first described in 1827 [2], is the most commonly diagnosed skin cancer worldwide [3]; comprising approximately 80% of NMSCs

  • The primary analysis of STEVIE demonstrated that vismodegib is tolerable in clinical practice and that long-term exposure is not associated with worsening severity or frequency of adverse events (AE)

  • This study reported that CD56 expression was significantly associated with risk of lack of response to vismodegib in advanced BCC cohort (OR = 5.5; 95% confidence interval (CI): 3.4–29.8; p = 0.0488), and a similar trend was observed for CXC receptor 4 (CXCR4) (OR = 3.45; 95% CI: 0.923–12.96; p = 0.066)

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Summary

Introduction

Non-melanoma skin cancers (NMSCs) include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), representing the most common cancers in the Caucasian population [1]. BCC, first described in 1827 [2], is the most commonly diagnosed skin cancer worldwide [3]; comprising approximately 80% of NMSCs. The incidence of BCC is increasing worldwide, by approximately 1% annually [4]. The increase in incidence of BCC could be due to changes in the environment or lifestyle risk factors. The most well-known risk factor is represented by solar ultraviolet (UV) exposure, especially early in life, or as a result of intermittent exposure. The multidisciplinary approach is critical in the management of patients suffering from BCC

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