Division of Dermatology, UCLA, 200 UCLA Medical Plaza, Los Angeles, CA, USA.
ILR Dermatology, Encino, CA, USA.
Curr Treat Options Oncol. 2019 Nov 26;20(11):84. doi: 10.1007/s11864-019-0683-9.
Advanced 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 syndrome 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 discontinuation 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, there are several new agents under investigation that may have improved efficacy for resistant tumors by utilizing different mechanisms of action than the two currently approved medications.
高级基底细胞癌 (BCC) 代表了一小部分 BCC，由于疗效不佳、高复发风险和过度发病率，这些 BCC 不适合标准治疗。Sonic hedgehog (Shh) 通路在 BCC 发展中的作用导致了系统 Shh 通路抑制剂的开发，为患有晚期 BCC 的患者提供了新的治疗选择和改善的生存机会。目前有两种获得美国食品和药物管理局 (FDA) 批准的 Shh 抑制剂，即 vismodegib 和 sonidegib，用于治疗晚期基底细胞癌。Vismodegib 获批用于局部晚期 BCC (laBCC) 和转移性 BCC (mBCC)，而 sonidegib 获批用于 laBCC。这些药物也已用于神经纤维瘤性基底细胞癌综合征的预防和手术前的新辅助治疗，我们认为 Shh 抑制剂在这些情况下的作用越来越大。缺乏比较 vismodegib 与 sonidegib 的头对头随机对照试验。不良事件可导致大多数患者停止治疗，从而限制这些药物的应用，因此，临床医生必须能够预测和管理最常见的副作用，如肌肉痉挛、脱发、味觉障碍、恶心和体重减轻。其他 Shh 抑制剂，包括抗真菌药物伊曲康唑，已在小型试验中进行了研究，但在推荐其常规临床使用之前，还需要进一步研究。此外，还有几种新的药物正在研究中，它们可能通过利用与目前两种批准药物不同的作用机制来提高对耐药肿瘤的疗效。
