Epigenetic therapy for mesothelioma is a new and evolving field. It builds upon the fact that one’s susceptibility to mesothelioma and other cancers is influenced by unique processes called epigenetic alterations. In the case of mesothelioma, these alterations are furthered by asbestos, acting directly on a cell’s DNA structure to affect how genes are expressed and regulated, ultimately leading to the development of mesothelioma. Epigenetic therapy for malignant pleural mesothelioma and malignant peritoneal mesothelioma hopes to use these epigenetic alterations as biomarkers to connect patients with the most effective therapies for their particular type of mesothelioma and unique genetic variation.
What Are the Different Types of Epigenetic Alterations and How Do They Relate to Mesothelioma?
There are four types of epigenetic alterations that have been found to involved in the development of mesothelioma:
- DNA methylation: an epigenetic mechanism in which extra methyl groups are added to a cell’s DNA. It is a normal process involved in gene expression and regulation. It impacts cancer development when the extra methyl groups are added to tumor suppressor genes, effectively inhibiting the cell’s built-in protection against cancer. DNA methylation is the main mechanism of epigenetic variation. It is observed to be overexpressed at specific sites and underexpressed overall in the DNA of individuals with mesothelioma. Individuals with the epithelial type of malignant pleural mesothelioma and less methylation have been observed to have longer survival rates. These individuals are also estimated to have a lower burden of cumulative asbestos exposure. Levels of DNA methylation can be analyzed in whole blood samples using a methylation array.
- Histone modification: an epigenetic mechanism in which gene expression is controlled by how tightly or loosely DNA is wrapped around proteins known as histones. Certain genes impacting histone modification are altered by asbestos exposure.
- Chromatin remodeling: an epigenetic mechanism in which the genes that code for protein complexes involved in remodeling genetic material are altered. These chromatin remodeling complexes are involved in other epigenetic processes.
- Non-coding RNAs: epigenetic regulators involved in gene silencing. These non-coding RNA molecules influence numerous cell functions implicated in cancer development.1
How Might Epigenetic Therapy Improve Mesothelioma Treatment?
Because epigenetic alterations play a key role in cancer development, it is hoped that greater study of these biomarkers might lead to the creation of more effective treatments for mesothelioma. Some anti-cancer drugs have already been developed to target histone modification, but these drugs have yet to be effective in treating malignant pleural mesothelioma when used as single agents. A mesothelioma drug that targets chromatin remodeling complexes could be especially effective because of these complexes’ involvement in multiple epigenetic processes. Epigenetic therapy holds promise for treating malignant pleural mesothelioma and malignant peritoneal mesothelioma, but more research needs to be done to transform this promise into reality.2
Epigenetic Therapy for Mesothelioma