At the National Centre of Asbestos Related Diseases (NCARD), we have produced many cutting-edge preclinical tools and models to support our research. These efforts are largely focused on the rare but deadly cancer, mesothelioma, caused by exposure to asbestos fibres. One such model is our MexTAg mice, which have been genetically engineered to study the development and progression of mesothelioma.
These mice have been modified in the laboratory so that their mesothelial cells are preconditioned to be susceptible to cancer. Mesothelial cells line the body cavities and are the cell type that develops into mesothelioma.
Importantly, MexTAg mice only develop mesothelioma after asbestos exposure. Equally importantly, all the asbestos-exposed MexTAg mice develop mesothelioma. These tumours are very similar to the mesothelioma that occurs in people following asbestos exposure.
Such genetically engineered mouse models, aptly called GEMs, are invaluable tools in our fight against mesothelioma. They allow us to investigate how asbestos causes cancer and test new treatment approaches in a living system that faithfully mimics the complexities of human disease.
They have been used in several mesothelioma-related studies, including those examining the effect of vitamin supplementation and exercise on the rare cancer.
Latest findings
In a recent study, our team used the MexTAg model to explore the genetic aspects of disease development. This research was published in Frontiers in Toxicology [read it here].
According to Dr Scott Fisher, one of the chief investigators, the project sought to uncover how one’s genes might affect susceptibility to developing mesothelioma after asbestos exposure.
Dr Scott Fisher. Image: NCARD.
“Despite ongoing research efforts, scientists still don’t fully understand how genetics influence the risk of developing mesothelioma, and we haven’t consistently identified any specific genes responsible for the disease,” Dr Fisher said.
A pioneering mouse model approach
Effective animal-based genetic studies require most individuals to develop the disease and sufficient genetic diversity in the study population to produce accurate results. Hence, it would be impractical to use normal laboratory mice for the study as they are inbred.
“We combined two powerful mouse models to overcome these limitations,” Dr Fisher explained.
“The first is the CC, or collaborative cross, a mouse resource that ensures maximum genetic variation for discovering genes that influence the disease of interest.
“The second is our well-characterised MexTAg mouse model, which ensures a high incidence of mesothelioma, but only after asbestos exposure.”
A novel framework for genetic discovery
Dr Fisher and the NCARD team found that genetics do indeed impact the development of asbestos-related diseases. However, genetics no longer had any effect after visible signs of disease appeared.
Rather than finding single genes responsible for mesothelioma, they identified several chromosomal regions associated with the disease. Although genes within these regions are known cancer risk modifiers, they have not previously been directly linked to mesothelioma.
“Researching the biological pathways associated with disease onset or progression will help unravel the complex biology of asbestos-related diseases and potentially identify new treatment targets.”
Dr Scott Fisher, NCARD
Notably, the study also showed that sophisticated mouse models are a viable way of overcoming hurdles inherent to studying rare human cancers with small study cohorts.