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Updated: Apr 28, 2026
Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
Patient with Gorlin syndrome and metastatic basal cell carcinoma refractory to smoothened inhibitors
Gefei A Zhu1, Angela S Li1, Anne Lynn S Chang1
1Department of Dermatology, Stanford University School of Medicine, Redwood City, California.
Importance:
Basal cell carcinomas (BCCs) in patients with Gorlin syndrome have been reported to be extremely sensitive to Smoothened (SMO) inhibitors, a novel targeted therapy against the Hedgehog pathway, because of characteristic mutations in these patients. A few cases of disease refractory to oral therapy with SMO inhibitors have been reported in patients with Gorlin syndrome and nonmetastatic BCCs, but refractory disease in distantly metastatic tumors has not been documented in this high-risk group.
Observations:
A man with Gorlin syndrome and innumerable cutaneous BCCs presented with biopsy-proven BCC in his lungs. After SMO inhibitor therapy, almost all of his cutaneous tumors shrank, but his lung metastases did not. These lung metastases remained refractory to treatment despite institution of a second SMO inhibitor.
Conclusions And Relevance:
We report a case of Gorlin syndrome in a patient with metastatic BCC refractory to SMO inhibitors. Furthermore, clinical responses in this patient's cutaneous tumors did not parallel the responses in the distant site. However, serial imaging after diagnosis of metastatic disease can be critical to monitor for response to therapy.
Insights
Metastatic basal cell carcinoma (BCC) in Gorlin syndrome patients can be resistant to Smoothened (SMO) inhibitors. This case highlights refractory lung metastases despite initial treatment response in cutaneous tumors.
Area of Science:
- Oncology
- Dermatology
- Genetics
Background:
- Gorlin syndrome is associated with numerous basal cell carcinomas (BCCs).
- Hedgehog pathway inhibitors, specifically Smoothened (SMO) inhibitors, are a novel targeted therapy for BCCs.
- Patients with Gorlin syndrome often exhibit characteristic mutations making BCCs sensitive to SMO inhibitors.
Observation:
- A patient with Gorlin syndrome and extensive cutaneous BCCs developed biopsy-proven lung metastases.
- Initial treatment with a SMO inhibitor led to significant shrinkage of cutaneous BCCs.
- Lung metastases remained unresponsive to the first SMO inhibitor and a subsequent second SMO inhibitor.
Findings:
- This case documents metastatic BCC in a Gorlin syndrome patient refractory to SMO inhibitor therapy.
- Clinical response of cutaneous tumors did not correlate with the response of distant lung metastases.
- The study highlights the potential for treatment resistance in advanced BCCs within this patient population.
Implications:
- Metastatic BCC in Gorlin syndrome may exhibit resistance to SMO inhibitors, challenging established treatment paradigms.
- Discrepant responses between primary and metastatic sites necessitate careful monitoring.
- Serial imaging is crucial for assessing therapeutic response in patients with metastatic BCC and Gorlin syndrome.
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