Targeted Epigenetic Modification to Improve Mesothelioma Responses to Immunotherapy
Abstract
The Fiscal Year 2019 Peer Reviewed Cancer Research Program Topic Areas are mesothelioma and immunotherapies. Mesothelioma is a cancer caused by asbestos that develops in the lining of the lungs. The prognosis is very poor, with 5-year survival rates of only 3% for men, and 12% for women. Immunotherapy is an exciting treatment for mesothelioma, because it can cause long-term tumor shrinkage. However, it only works exceptionally well for approximately 20% of cancer patients, but not others. We want to improve the number of mesothelioma patients that benefit from immunotherapy. Genes can be switched on and off through a process called epigenetic modification, and individual genes and their respective switches have been mapped in mesothelioma. Important immune genes in mesothelioma tumors are often switched off, which may explain why immunotherapy does not work well in some patients. Current drugs change these switches irrespective of the genes, possibly switching on genes that should not be switched on. Hence, current epigenetic drugs have potential toxic side effects, and do not work well in mesothelioma. We have developed a new technology that allows us to selectively switch on the genes that we want in cells. We will test this technology in mouse mesothelioma tumors. We will switch on important immune genes and use mouse models to test if immunotherapy will work better against these modified tumors. The long-term application of our research is to use this technology with immunotherapy for mesothelioma patients, with the goal of turning a non-responding patient to a responding one. This is a first of its kind study in mesothelioma. If our project is successful, the next step would be to test our technology in human mesothelioma cells, and we anticipate that it will take at least 5-10 years before a clinically relevant outcome is achieved. Furthermore, our study will significantly contribute to cancer research as the technology can be tailored to switch on/off other genes within tumors. It can be potentially used to improve other cancer therapies, such as chemotherapy and radiotherapy, ultimately benefiting mesothelioma patients. In particular, our research will benefit Veterans and their family members who have contracted mesothelioma because of previous exposure to asbestos. Furthermore, countries such as Iraq and Afghanistan are still using asbestos in construction, exposing currently deployed troops to this carcinogen. Treatment for malignant mesothelioma is poor, with chemotherapy giving a median survival of 12 months. As immunotherapy is currently being fast-tracked into the clinic for different cancers, including mesothelioma, we expect to see more Veterans and family members with mesothelioma being treated with immunotherapy, and our research will benefit them. Apart from reducing their exposure to asbestos, medical research into improving mesothelioma treatment is the most useful way to benefit Service members and their family members who have mesothelioma.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010621
Entities
People
- Anna K. Nowak
Organizations
- United States Army
- University of Western Australia