Sonic Hedgehog Pathway Inhibition in the Treatment of Advanced Basal Cell Carcinoma

Opinion statementAdvanced basal cell carcinoma (BCC) represents a small proportion of BCCs that are not amenable to standard therapies due to lack of efficacy, high recurrence risk, and excessive morbidity. Implication of the Sonic hedgehog (Shh) pathway in the development of BCC has led to the development of systemic Shh pathway inhibitors, providing patients with advanced BCCs new treatment options and improved survival. There are currently two Food and Drug Administration (FDA) –approved Shh inhibitors, vismodegib and sonidegib, for advanced basal cell carcinomas. Vismodegib has approval for locally advanced BCCs (laBCC) and metastatic BCC (mBCC), while sonidegib has approval for laBCC. These agents have also been used for prevention in nevoid basal cell carcinoma syndro me and as neoadjuvant therapy before surgery, and we feel that there is a growing role of Shh inhibitors in these settings. Head-to-head randomized controlled trials comparing vismodegib to sonidegib are lacking. Adverse events can limit the utility of these medications by leading to treatment disco ntinuation in a large proportion of patients, and it is thus essential that prescribers be able to anticipate and manage the most frequent side effects of muscle spasms, alopecia, dysgeusia, nausea, and weight loss. Other Shh inhibitors, including the antifungal itraconazole, have been investigated in small trials, but further research is needed before recommending their routine clinical use. Additionally, th...
Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research