Analysis of residual disease in periocular basal cell carcinoma following hedgehog pathway inhibition: Follow up to the VISORB trial
Basal cell carcinoma (BCC) is a common skin cancer caused by deregulated hedgehog signaling. BCC is often curable surgically; however, for orbital and periocular BCCs (opBCC), surgical excision may put visual function at risk. Our recent clinical trial highlighted the utility of vismodegib for prese...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714843/?tool=EBI |
| _version_ | 1811178453789048832 |
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| author | Shelby P. Unsworth Christina F. Tingle Curtis J. Heisel Emily A. Eton Christopher A. Andrews May P. Chan Scott C. Bresler Alon Kahana |
| author_facet | Shelby P. Unsworth Christina F. Tingle Curtis J. Heisel Emily A. Eton Christopher A. Andrews May P. Chan Scott C. Bresler Alon Kahana |
| author_sort | Shelby P. Unsworth |
| collection | DOAJ |
| description | Basal cell carcinoma (BCC) is a common skin cancer caused by deregulated hedgehog signaling. BCC is often curable surgically; however, for orbital and periocular BCCs (opBCC), surgical excision may put visual function at risk. Our recent clinical trial highlighted the utility of vismodegib for preserving visual organs in opBCC patients: 67% of patients displayed a complete response histologically. However, further analysis of excision samples uncovered keratin positive, hedgehog active (Gli1 positive), proliferative micro-tumors. Sequencing of pre-treatment tumors revealed resistance conferring mutations present at low frequency. In addition, one patient with a low-frequency SMO W535L mutation recurred two years post study despite no clinical evidence of residual disease. Sequencing of this recurrent tumor revealed an enrichment for the SMO W535L mutation, revealing that vismodegib treatment enriched for resistant cells undetectable by traditional histology. In the age of targeted therapies, linking molecular genetic analysis to prospective clinical trials may be necessary to provide mechanistic understanding of clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02436408. |
| first_indexed | 2024-04-11T06:19:43Z |
| format | Article |
| id | doaj.art-75630afe085345baaf082d245823f304 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T06:19:43Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-75630afe085345baaf082d245823f3042022-12-22T04:40:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011712Analysis of residual disease in periocular basal cell carcinoma following hedgehog pathway inhibition: Follow up to the VISORB trialShelby P. UnsworthChristina F. TingleCurtis J. HeiselEmily A. EtonChristopher A. AndrewsMay P. ChanScott C. BreslerAlon KahanaBasal cell carcinoma (BCC) is a common skin cancer caused by deregulated hedgehog signaling. BCC is often curable surgically; however, for orbital and periocular BCCs (opBCC), surgical excision may put visual function at risk. Our recent clinical trial highlighted the utility of vismodegib for preserving visual organs in opBCC patients: 67% of patients displayed a complete response histologically. However, further analysis of excision samples uncovered keratin positive, hedgehog active (Gli1 positive), proliferative micro-tumors. Sequencing of pre-treatment tumors revealed resistance conferring mutations present at low frequency. In addition, one patient with a low-frequency SMO W535L mutation recurred two years post study despite no clinical evidence of residual disease. Sequencing of this recurrent tumor revealed an enrichment for the SMO W535L mutation, revealing that vismodegib treatment enriched for resistant cells undetectable by traditional histology. In the age of targeted therapies, linking molecular genetic analysis to prospective clinical trials may be necessary to provide mechanistic understanding of clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02436408.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714843/?tool=EBI |
| spellingShingle | Shelby P. Unsworth Christina F. Tingle Curtis J. Heisel Emily A. Eton Christopher A. Andrews May P. Chan Scott C. Bresler Alon Kahana Analysis of residual disease in periocular basal cell carcinoma following hedgehog pathway inhibition: Follow up to the VISORB trial PLoS ONE |
| title | Analysis of residual disease in periocular basal cell carcinoma following hedgehog pathway inhibition: Follow up to the VISORB trial |
| title_full | Analysis of residual disease in periocular basal cell carcinoma following hedgehog pathway inhibition: Follow up to the VISORB trial |
| title_fullStr | Analysis of residual disease in periocular basal cell carcinoma following hedgehog pathway inhibition: Follow up to the VISORB trial |
| title_full_unstemmed | Analysis of residual disease in periocular basal cell carcinoma following hedgehog pathway inhibition: Follow up to the VISORB trial |
| title_short | Analysis of residual disease in periocular basal cell carcinoma following hedgehog pathway inhibition: Follow up to the VISORB trial |
| title_sort | analysis of residual disease in periocular basal cell carcinoma following hedgehog pathway inhibition follow up to the visorb trial |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714843/?tool=EBI |
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