Answer: D: Oral therapy for this disease targets smoothened.
This image shows a classic rodent ulcer of basal cell carcinoma (BCC). The overall risk of metastasis in all BCCs is quite low, 0.028-0.55%. However, large, ulcerated BCCs have a higher risk of metastasis. The risk of metastasis is 1.9% for BCCs greater than 3.0 cm and up to 45.0% for BCCs greater than 10 cm.
Two hedgehog pathway inhibitors, vismodegib and sonidegib are approved for the treatment of BCCs in patients who are not candidates for surgery or radiation, or whose disease has recurred after surgery. Only vismodegib is approved for the treatment of metastatic BCCs. Both drugs inhibit smoothened. Patched is mutated in BCCs and therefore does not suppress Smoothened signaling.
P53 is mutated in squamous cell carcinomas and some melanomas. Imatinib, an inhibitor of protein tyrosine kinase, targets the t(17;22) chromosome translocation resulting in fusion of COL1A1 with the PDGFB gene. This translocation is present in 90% of dermatofibroma sarcoma protuberans. Ipilimumab targets cytotoxic T-lymphocyte antigen 4 (CTLA-4). Ipilimumab is used as a treatment for unresectable or metastatic melanoma.
Kwon GP, Ally MS, Bailey-Healy I, Oro AE, Kim J, Chang AL, et al. Update to an open-label clinical trial of vismodegib as neoadjuvant before surgery for high-risk basal cell carcinoma (BCC). J Am Acad Dermatol 2016;75(1):213-5.
Migden MR, Guminski A, Gutzmer R, Dirix L, Lewis KD, Combemale P, et al. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. Lancet Oncol 2015;16(6):716-28.
Snow SN, Sahl W, Lo JS et al. Metastatic basal cell carcinoma. Report of five cases. Cancer 1994; 73: 328–335.
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