ABSTRACT
Introduction
Mesothelioma is an aggressive mesothelial lining tumor. Available drug therapies include chemotherapeutic agents, targeted molecular therapies, and immune system modulators. Mouse models were instrumental in the discovery and evaluation of such therapies, but there is need for improved understanding of the role of inflammation, tumor heterogeneity, mechanisms of carcinogenesis, and the tumor microenvironment. Novel mouse models may provide new insights and drive drug therapy discovery that improves efficacy.
Areas covered
This review concerns available mouse models for mesothelioma drug discovery and development including the advantages and disadvantages of each. Gaps in current knowledge of mesothelioma are highlighted, and future directions for mouse model research are considered.
Expert opinion
Soon, CRISPR-Cas gene-editing will improve understanding of mesothelioma mechanisms foundational to the discovery and testing of efficacious therapeutic targets. There are at least two likely areas of upcoming methodology development. One is concerned with precise modeling of inflammation - is it a causal process whereby inflammatory signals contribute to tumor initiation, or is it a secondary passenger process driven by asbestos exposure effects? The other area of methods improvement regards the availability of humanized immunocompromised mice harboring patient-derived xenografts. Combining human tumors in an environment with human immune cells will enable rapid innovation in immuno-oncology therapeutics.
Article highlights
Many drug therapies have been tested against mesothelioma with overall poor survival results necessitating the discovery of novel agents with improved efficacy
Several mouse models are available: 1) asbestos induction, 2) genetically engineered models, and 3) graft models, including patient-derived xenografts
No single model accurately represents human disease, and each model has its advantages and disadvantages
Current gaps in our knowledge of mesothelioma include the role of inflammation, tumor heterogeneity, mechanisms of carcinogenesis, and the tumor microenvironment
Novel mouse models are needed to better understand the pathophysiology of mesothelioma, with CRISPR genome editing and humanized patient-derived xenograft models as likely future avenues for innovative drug testing and development
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Declaration of interest
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer Disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.