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Treatment of resectable metastases is typically limited to invasive surgery with adjuvant radiotherapy; however, many patients fail to respond and there is minimal data to predict response or propose effective alternatives. Precision medicine could improve this, though genomic biomarkers remain elusive in the high mutational background and genomic complexity of cSCC. A phenotypic approach to precision medicine using patient\u2010derived ex\u00a0vivo tumour models is gaining favour for its capacity to directly assess biological responses to therapeutics as a functional, predictive biomarker. However, the use of ex\u00a0vivo models for guiding therapeutic selection has yet to be employed for metastatic cSCC. This review will therefore evaluate the existing experimental models of metastatic cSCC and discuss how ex\u00a0vivo methods could overcome the shortcomings of these existing models. Disease\u2010specific considerations for a prospective methodological pipeline will also be discussed in the context of precision medicine.<\/jats:p>","DOI":"10.1111\/exd.15089","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T06:24:46Z","timestamp":1714026286000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1016-1710","authenticated-orcid":false,"given":"Jessica","family":"Conley","sequence":"first","affiliation":[{"name":"Faculty of Science, Medicine and Health, School of Chemistry and Molecular Bioscience, Molecular Horizons University of Wollongong  Wollongong New South Wales 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