Use of preclinical models for malignant pleural mesothelioma

Abstract

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 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 three-dimensional 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. 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.

Keywords: asbestos induced lung disease; mesothelioma; pleural disease.

Figure 1

Current and potential future three-dimensional (3D) models of malignant pleural mesothelioma (MPM). (A) Spheroids are obtained by culturing the cell lines or dissected primary tissues as small as 1 mm on a non-adherent or low-adherent plate. (B) Microfluidic chips are implemented to model MPM using cell line-derived spheroids or digested tumour tissue from patients. Arrows shows the medium flow. (C) Potential future 3D model of organoids is obtained using defined medium and a 3D matrix.