{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T20:57:48Z","timestamp":1762981068099,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer. Most patients who develop metastases (2\u20135%) 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.<\/jats:p>","DOI":"10.3390\/ijms21249536","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T21:11:02Z","timestamp":1608066662000},"page":"9536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Comprehensive Mutational and Phenotypic Characterization of New Metastatic Cutaneous Squamous Cell Carcinoma Cell Lines Reveal Novel Drug Susceptibilities"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1153-4609","authenticated-orcid":false,"given":"Jay","family":"Perry","sequence":"first","affiliation":[{"name":"Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW 2522, Australia"},{"name":"Illawarra Health &amp; Medical Research Institute, Wollongong, NSW 2522, Australia"},{"name":"CONCERT Translational Cancer Research Centre, Liverpool, NSW 2170, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4547-6611","authenticated-orcid":false,"given":"Bruce","family":"Ashford","sequence":"additional","affiliation":[{"name":"Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW 2522, Australia"},{"name":"Illawarra Health &amp; Medical Research Institute, Wollongong, NSW 2522, Australia"},{"name":"CONCERT Translational Cancer Research Centre, Liverpool, NSW 2170, Australia"},{"name":"Sydney Head and Neck Cancer Institute, Chris O\u2019Brien Lifehouse, Camperdown, NSW 2050, Australia"},{"name":"School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4592-0380","authenticated-orcid":false,"given":"Amarinder Singh","family":"Thind","sequence":"additional","affiliation":[{"name":"Illawarra Health &amp; Medical Research Institute, Wollongong, NSW 2522, Australia"},{"name":"School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Emilie","family":"Gauthier","sequence":"additional","affiliation":[{"name":"Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8674-6801","authenticated-orcid":false,"given":"Elahe","family":"Minaei","sequence":"additional","affiliation":[{"name":"Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW 2522, Australia"},{"name":"Illawarra Health &amp; Medical Research Institute, Wollongong, NSW 2522, Australia"},{"name":"CONCERT Translational Cancer Research Centre, Liverpool, NSW 2170, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4275-4199","authenticated-orcid":false,"given":"Gretel","family":"Major","sequence":"additional","affiliation":[{"name":"Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW 2522, Australia"},{"name":"Illawarra Health &amp; Medical Research Institute, Wollongong, NSW 2522, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narayanan Gopalakrishna","family":"Iyer","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruta","family":"Gupta","sequence":"additional","affiliation":[{"name":"Sydney Head and Neck Cancer Institute, Chris O\u2019Brien Lifehouse, Camperdown, NSW 2050, Australia"},{"name":"Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, NSW Health Pathology, Camperdown, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Clark","sequence":"additional","affiliation":[{"name":"Sydney Head and Neck Cancer Institute, Chris O\u2019Brien Lifehouse, Camperdown, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5570-9645","authenticated-orcid":false,"given":"Marie","family":"Ranson","sequence":"additional","affiliation":[{"name":"Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW 2522, Australia"},{"name":"Illawarra Health &amp; 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