Clapper, Patti, Schweizer and Mason

A recent study out of Australia describes how the transgenic MexTAg mouse develops asbestos-induced mesothelioma in ways similar to humans, and therefore is an excellent model for exploring the characteristics of mesothelioma as well as testing a wide range of treatments for mesothelioma.  Ultimately, the use of such mice could lead to finding a therapy that would actually prevent the development of mesothelioma in asbestos-exposed populations.

Mice have been used in medical research for many years.  The first successful gene transfers into mice began in 1980, and since that time researchers have used transgenic mice to observe the role genes play in development of diseases.  Transgenic mice are predictable models that can be reproduced with efficiency in a short period of time that makes them very useful for research, including clinical trials investigating new treatments for mesothelioma.

This study from the National Centre for Asbestos Related Diseases (NCARD) and the University of Western Australia was investigating whether  MexTAg mice who were exposed to asbestos develop mesothelioma in ways that replicate the key features of human forms of the disease.  Upon conclusion, they found that indeed transgenic mice are a suitable, translatable clinical model that can be used for screening a wide variety of treatment protocols.  This is especially good news since mesothelioma is relatively rare and no other biological druggable targets exist to test out toxicity, dose, scheduling and efficacy of potential preventive therapies.

Mesothelioma is caused by exposure to asbestos and has a long latency period of 10 to 50 years from time of exposure to development of symptoms.  The median survival from time of diagnosis is less than a year.  To date, treatment Is palliative and there is no known cure.  Because of the characteristics and rarity of mesothelioma, alternative models that replicate human mesothelioma are needed to investigate chemopreventative strategies.

During the study, researchers found that MexTAg mice not exposed to asbestos did not develop mesothelioma, however 100% of those exposed to asbestos developed the disease within 20 to 40 weeks from time of exposure.  Researchers discovered that the neither the age nor gender of the mouse were prognostic factors.    They did however find that the older the mouse at time of diagnosis, the poorer prognosis, similar to human patients.

In addition, researchers found similarities between mouse and human mesothelioma in terms of tumor location, latency period, and response to long term treatment with a cytotoxic drug.   They also suggest that COX-2 inhibitors administered prior to development of mesothelioma does not have any survival benefit and therefore is not a useful prevention therapy to be used with populations with known history of prior asbestos exposure.

The study suggests that the MexTAg mouse model is optimal for testing preventative agents and new therapies that could prevent or treat mesothelioma.  Researchers also suggest that this model could be used to test multiple irritants (such as exposing mice not only to asbestos but also to other toxins) to determine how exposures to other substances affect the development of mesothelioma.  This particular study found that other irritants alone did not induce mesothelioma, and focused on mice exposed to asbestos only. 

The ultimate goal would be to use the mice to discover a therapy that could actually prevent the development of mesothelioma in populations that had known exposure.  The model could also be used to see which drugs play significantly beneficial roles in slowing disease progression and improving survival times, and which combination therapies work best towards achieving these ends.