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Comprehensive mutational and phenotypic characterization of new metastatic cutaneous squamous cell carcinoma cell lines reveal novel drug susceptibilities

Journal Article


Abstract


  • Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer. Most patients who develop metastases (2–5%) present with advanced disease that requires a combination of radical surgery and adjuvant radiation therapy. There are few effective therapies for refractory disease. In this study, we describe novel patient-derived cell lines from cSCC metastases of the head and neck (designated UW-CSCC1 and UW-CSCC2). The cell lines genotypically and phenotypically resembled the original patient tumor and were tumorogenic in mice. Differences in cancer-related gene expression between the tumor and cell lines after various culturing conditions could be largely reversed by xenografting and reculturing. The novel drug susceptibilities of UW-CSCC1 and an irradiated subclone UW-CSCC1-R to drugs targeting cell cycle, PI3K/AKT/mTOR, and DNA damage pathways were observed using high-throughput anti-cancer and kinase-inhibitor compound libraries, which correlate with either copy number variations, targetable mutations and/or the upregulation of gene expression. A secondary screen of top hits in all three cell lines including PIK3CA-targeting drugs supports the utility of targeting the PI3K/AKT/mTOR pathway in this disease. UW-CSCC cell lines are thus useful preclinical models for determining targetable pathways and candidate therapeutics.

Publication Date


  • 2020

Citation


  • Perry, J., Ashford, B., Thind, A. S., Gauthier, M. E., Minaei, E., Major, G., . . . Ranson, M. (2020). Comprehensive mutational and phenotypic characterization of new metastatic cutaneous squamous cell carcinoma cell lines reveal novel drug susceptibilities. International Journal of Molecular Sciences, 21(24), 1-17. doi:10.3390/ijms21249536

Scopus Eid


  • 2-s2.0-85098149605

Start Page


  • 1

End Page


  • 17

Volume


  • 21

Issue


  • 24

Abstract


  • Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer. Most patients who develop metastases (2–5%) present with advanced disease that requires a combination of radical surgery and adjuvant radiation therapy. There are few effective therapies for refractory disease. In this study, we describe novel patient-derived cell lines from cSCC metastases of the head and neck (designated UW-CSCC1 and UW-CSCC2). The cell lines genotypically and phenotypically resembled the original patient tumor and were tumorogenic in mice. Differences in cancer-related gene expression between the tumor and cell lines after various culturing conditions could be largely reversed by xenografting and reculturing. The novel drug susceptibilities of UW-CSCC1 and an irradiated subclone UW-CSCC1-R to drugs targeting cell cycle, PI3K/AKT/mTOR, and DNA damage pathways were observed using high-throughput anti-cancer and kinase-inhibitor compound libraries, which correlate with either copy number variations, targetable mutations and/or the upregulation of gene expression. A secondary screen of top hits in all three cell lines including PIK3CA-targeting drugs supports the utility of targeting the PI3K/AKT/mTOR pathway in this disease. UW-CSCC cell lines are thus useful preclinical models for determining targetable pathways and candidate therapeutics.

Publication Date


  • 2020

Citation


  • Perry, J., Ashford, B., Thind, A. S., Gauthier, M. E., Minaei, E., Major, G., . . . Ranson, M. (2020). Comprehensive mutational and phenotypic characterization of new metastatic cutaneous squamous cell carcinoma cell lines reveal novel drug susceptibilities. International Journal of Molecular Sciences, 21(24), 1-17. doi:10.3390/ijms21249536

Scopus Eid


  • 2-s2.0-85098149605

Start Page


  • 1

End Page


  • 17

Volume


  • 21

Issue


  • 24