Use of preclinical models for malignant pleural mesothelioma.
Garnett, Mathew J
Francies, Hayley Elizabeth
BMJ Publishing Group
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Shamseddin, M., Obacz, J., Garnett, M. J., Rintoul, R., Francies, H. E., & Marciniak, S. (2021). Use of preclinical models for malignant pleural mesothelioma.. Thorax https://doi.org/10.1136/thoraxjnl-2020-216602
Malignant pleural mesothelioma (MPM) is an aggressive cancer most commonly caused by prior exposure to asbestos. Median survival is 12-18 months, since surgery is ineffective and chemotherapy offers minimal benefit. Preclinical models that faithfully recapitulate the genomic and histopathological features of cancer are critical for the development of new treatments. The most commonly used models of MPM are two-dimensional (2D) cell lines established from primary tumours or pleural fluid. While these have provided some important insights into MPM biology, these cell models have significant limitations. In order to address some of these limitations spheroids and microfluidic chips have more recently been used to investigate the role of the 3D environment in MPM. Efforts have also been made to develop animal models of MPM, including asbestos-induced murine tumour models, MPM-prone genetically modified mice, and patient derived xenografts (PDX). Here we discuss the available in vitro and in vivo models of MPM and highlight their strengths and limitations. We discuss how newer technologies, such as the tumour-derived organoids, might allow us to address the limitations of existing models and aid in the identification of effective treatments for this challenging to treat disease.
MS and JO are supported by BLF-Papworth Fellowships from the British Lung Foundation and the Victor Dahdaleh Foundation. MJG and HEF is supported by the British Lung Foundation and Wellcome Trust grant 206194. RCR is supported by the Cambridge Biomedical Research Centre, Cancer Research UK Cambridge Centre, British Lung Foundation and Royal Papworth Hospital. SJM is supported by the Medical Research Council, British Lung Foundation, Cambridge BRC, Royal Papworth Hospital, and the Alpha1-Foundation
External DOI: https://doi.org/10.1136/thoraxjnl-2020-216602
This record's URL: https://www.repository.cam.ac.uk/handle/1810/318315
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