Analysis of residual disease in periocular basal cell carcinoma following hedgehog pathway inhibition: Follow up to the VISORB trial.
PLoS One
; 17(12): e0265212, 2022.
Article
em En
| MEDLINE
| ID: mdl-36455049
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Basocelular
/
Neoplasia de Células Basais
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos