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Published on: February 28, 2014
Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical
Jessica Conley1, Jay R Perry1, Bruce Ashford2
1Faculty of Science, Medicine and Health, School of Chemistry and Molecular Bioscience, Molecular Horizons, University of Wollongong, Wollongong, New South Wales, Australia.
Abstract:
Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy worldwide, with most deaths caused by locally advanced and metastatic disease. 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-derived ex vivo 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 vivo 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 vivo methods could overcome the shortcomings of these existing models. Disease-specific considerations for a prospective methodological pipeline will also be discussed in the context of precision medicine.
Insights
Precision medicine for cutaneous squamous cell carcinoma (cSCC) needs better predictive biomarkers. Patient-derived ex vivo tumor models offer a promising phenotypic approach to guide treatment for metastatic cSCC.
Area of Science:
- Oncology
- Translational Medicine
Background:
- Cutaneous squamous cell carcinoma (cSCC) is a prevalent malignancy, with advanced and metastatic forms causing significant mortality.
- Current treatments for metastatic cSCC, including surgery and radiotherapy, have limited efficacy and lack predictive biomarkers for patient response.
- Genomic biomarkers for precision medicine in cSCC are challenging due to high mutational burden and complexity.
Purpose of the Study:
- To review existing experimental models for metastatic cSCC.
- To explore the potential of patient-derived ex vivo tumor models for precision medicine in metastatic cSCC.
- To discuss the application of ex vivo models in overcoming limitations of current experimental models and guiding therapeutic selection.
Main Methods:
- Literature review of experimental models for metastatic cSCC.
- Evaluation of phenotypic approaches using patient-derived ex vivo tumor models.
- Discussion of methodological considerations for implementing ex vivo models in a precision medicine context.
Main Results:
- Existing models for metastatic cSCC have limitations in predicting clinical response.
- Ex vivo tumor models provide a functional, predictive biomarker by directly assessing therapeutic responses.
- Patient-derived ex vivo models are underutilized but hold significant potential for guiding treatment in metastatic cSCC.
Conclusions:
- Ex vivo tumor models represent a viable phenotypic strategy for advancing precision medicine in metastatic cSCC.
- This approach can overcome the limitations of current models and improve therapeutic selection for patients.
- Further development of a methodological pipeline is needed to integrate ex vivo models into clinical practice for cSCC.
