Clapper, Patti, Schweizer and Mason

Exposure to asbestos is the main causative factor for mesothelioma, a form of cancer that develops in the internal organs of the body and is very difficult to diagnose and treat.  Clinical researchers have been exploring new avenues that would enable earlier diagnosis and extend overall survival times for mesothelioma patients.  One area of exploration is gene therapy.  A recent study from the Juntendo University School of Medicine in Tokyo, Japan investigated the role mesothelin (MSLN) plays in the development and progression of mesothelioma.

Mesothelin is a differentiation antigen that has been found to be overexpressed in mesothelioma as well as other cancers.  Clinical studies have shown evidence that mesothelin is an immunogenic protein and that, in its soluble form, could be used as a tumor marker and possible vaccine for malignant mesotheliomas.  In addition to cytologic examinations, clinicians have begun to use soluble mesothelin-related proteins (SMRP) to identify people with mesothelioma and to monitor their progress. 

Researchers from Japan showed that a mesothelin promoter is hypomethylated in patients with mesothelioma.  This suggests that there is some mechanism that suppresses mesothelin expression and makes the patient more susceptible to malignancy.   Methylation could be further understood as chemical modification of DNA or genes. Some methylation acts as an epigenetic event that can lead to gene silencing, which is basically equivalent to deleting the gene.  DNA methylation is a common mechanism of inactivation of tumor suppressor genes.

Tumor suppressor genes are important because they can prevent cells from transforming into malignancy in several ways:

·         protect the gene and DNA from mutating

·         deregulates cell progression

·         induces apoptosis, or cell death

·         inhibits cell migration and metastasis

All these interfere with malignant transformation, and if this is suppressed, tumors are more likely to occur, as in the case of mesothelioma.    Further studies are needed to understand the mechanisms that are interfering with mesothelin expression in patients diagnosed with mesothelioma, and to explore ways to use this information to create adjuvant therapies that could treat the disease.