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Orthotopic Implantation and Peripheral Immune Cell Monitoring in the II-45 Syngeneic Rat Mesothelioma Model
Published on: October 2, 2015
Mouse models for mesothelioma drug discovery and development
Kenneth P Seastedt1, Nathanael Pruett2, Chuong D Hoang2
1Department of Surgery, Uniformed Services University of the Health Sciences F. Edward Hébert School of Medicine, Bethesda, Maryland, USA.
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.
Insights
Mouse models are crucial for mesothelioma drug discovery, but new models are needed to understand inflammation and tumor complexity. Future models, including CRISPR-Cas and humanized mice, will accelerate the development of more effective mesothelioma therapies.
Area of Science:
- Oncology
- Translational Research
Background:
- Mesothelioma is an aggressive cancer of the mesothelial lining.
- Current drug therapies include chemotherapy, targeted therapy, and immunotherapy.
- Existing mouse models have limitations in fully recapitulating mesothelioma's complexity.
Purpose of the Study:
- To review available mouse models for mesothelioma drug discovery.
- To identify knowledge gaps in mesothelioma research.
- To consider future directions for mouse model development.
Main Methods:
- Review of existing literature on mesothelioma mouse models.
- Discussion of advantages and disadvantages of various models.
- Exploration of emerging technologies like CRISPR-Cas and humanized mice.
Main Results:
- Mouse models have been vital for evaluating mesothelioma therapies.
- Gaps exist in understanding inflammation, tumor heterogeneity, carcinogenesis, and the tumor microenvironment.
- Novel mouse models are essential for advancing mesothelioma treatment.
Conclusions:
- CRISPR-Cas gene editing will enhance understanding of mesothelioma mechanisms.
- Precise modeling of inflammation's role in mesothelioma is needed.
- Humanized mouse models with patient-derived xenografts will drive immuno-oncology innovation.

