Therapeutic Approaches for Advanced Basal Cell Carcinoma: A Comprehensive Review

Area of Science:

• Dermatology
• Oncology
• Molecular Biology

Background:

• Basal cell carcinoma (BCC) is the most common skin cancer, often curable by excision.
• Advanced or difficult-to-treat BCC poses significant therapeutic challenges when surgery or radiotherapy are not optimal.

Purpose of the Study:

• To review the molecular mechanisms underlying BCC development.
• To define advanced/difficult-to-treat BCC.
• To summarize current and emerging systemic treatment options for BCC.

Main Methods:

• Literature review focusing on molecular pathogenesis of BCC.
• Analysis of pivotal clinical trial data for approved hedgehog inhibitors (sonidegib and vismodegib).
• Exploration of novel therapeutic strategies, including neoadjuvant and combination therapies.

Main Results:

• Hedgehog pathway inhibitors (HHI) like sonidegib and vismodegib represent key systemic treatments for advanced BCC.
• Comparison of pivotal trial data highlights efficacy and safety profiles of approved HHIs.
• Emerging neoadjuvant and combination approaches show promise for difficult-to-treat BCC.

Conclusions:

• Understanding BCC molecular pathogenesis is crucial for targeted therapy.
• Systemic treatments, particularly HHIs, have transformed advanced BCC management.
• Future directions involve novel combinations and neoadjuvant strategies to improve outcomes in challenging BCC cases.