Vismodegib and Sonidegib in Locally Advanced and Metastatic Basal Cell Carcinoma: Update on Hedgehog Pathway Inhibitors

Actas Dermosifiliogr. 2022 May;113(5):443-450. doi: 10.1016/j.ad.2022.01.005. Epub 2022 Jan 31.
[Article in English, Spanish]

Abstract

As one of the most common malignancies, basal cell carcinoma (BCC) has evolved as a global burden with incidence annually rising, especially in the older population. Even though the condition is mostly localized, the nature of the disease is destructive and can evolve as either locally advanced BCC (laBCC) or even more rarely as metastatic BCC (mBCC). There are well-established conventional treatment options for these cases, including surgeries and radiotherapy. However, not all cases are eligible for conventional treatments. Recently, biologic treatment has gained a lot of attention and research. This has led to the development of targeted treatment involving the hedgehog pathway inhibitor (HPI), a key pathogenesis in laBCC and mBCC. There are currently two approved HPIs, vismodegib and sonidegib to treat inoperable laBCC and mBCC. This review seeks to explore the pathophysiology of hedgehog pathway behind the development of BCC, and the current update of the efficacy as well as pharmacokinetics properties of HPIs that led to the ideal treatment for laBCC or mBCC, either as monotherapy or in combination with other conventional therapies.

Keywords: Carcinoma basocelular localmente avanzado; Carcinoma basocelular metastásico; Hedgehog pathway inhibitor; Inhibidores de la vía de Hedgehog; Locally advanced basal cell carcinoma; Metastatic basal cell carcinoma; Sonidegib; Vismodegib.

Publication types

  • Review

MeSH terms

  • Anilides / adverse effects
  • Antineoplastic Agents* / adverse effects
  • Biphenyl Compounds
  • Carcinoma, Basal Cell* / drug therapy
  • Carcinoma, Basal Cell* / pathology
  • Hedgehog Proteins / metabolism
  • Hedgehog Proteins / therapeutic use
  • Humans
  • Pyridines
  • Skin Neoplasms* / drug therapy
  • Skin Neoplasms* / pathology

Substances

  • Anilides
  • Antineoplastic Agents
  • Biphenyl Compounds
  • Hedgehog Proteins
  • HhAntag691
  • Pyridines
  • sonidegib