Mesothelioma Genetic Testing, Gene Therapy and Gene Expression

Is Mesothelioma Genetic?

Asbestos is the only proven cause of mesothelioma, but not everyone exposed to asbestos develops this cancer. In fact, most exposed people are not affected.

Researchers continue to study genetic factors that may one day explain why some individuals are more susceptible to developing this disease and why treatment responses vary from patient to patient.

Studying the genetic and molecular characteristics of mesothelioma cells may lead to more personalized treatment approaches and new therapies that will be able to target the unique features in a patient’s specific mesothelioma cancer cells.

Benefits of Mesothelioma Genetic Testing and Research

Asbestos causes mesothelioma when microscopic asbestos fibers are either inhaled or ingested into the body. These fibers can get embedded into tissue cells and eventually cause alterations in the cell’s DNA. This disruption of genetic balance leads to cells duplicating faster, living longer, and forming clumps that create tumors. It all starts when asbestos fibers disrupt the cell’s genetic makeup.

This is why genetic testing is so crucial to people diagnosed with mesothelioma — and for doctors trying to solve the riddle of this rare cancer. No two people will have the exact same mesothelioma, especially at the molecular level.

Dr. Ezra Cohen, an oncologist at University of California San Diego Health, treats pleural mesothelioma. He said genetic testing and research on a patient-by-patient level is essential. It can provide information on genetic mutations, expression and the tumor microenvironment.

For instance, each patient will have different levels of gene and protein expression on the diseased cells and in the tumors. Some therapies, such as immunotherapy, are created to specifically target these genes and proteins.

Measuring a person’s gene and protein expression may lead to an individualized treatment regimen. This can be effective in controlling each patient’s unique cancer. Gene analysis can also help doctors provide a more precise prognosis.

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Mesothelioma Genes and Proteins

Genes are made of DNA and act like an instruction manual for cells. When cells need necessary proteins to survive they create a temporary RNA copy of the gene’s instructions. The cell then uses these instructions to build the protein. If a gene is mutated, the cell may make too much, too little, or an abnormal version of the protein – which can contribute to the development of diseases and cancer.

Asbestos causes a series of harmful changes in mesothelial cells that can eventually lead to mesothelioma. The changes start when asbestos fibers create chronic inflammation in healthy mesothelial cells, cause alterations in the cell’s DNA, disrupt cell growth and duplication, and cause cell death.  When healthy cells are replaced by mutated cells there can be an underexpression or overexpression of necessary genes and proteins which can lead to rampant cell division and can cause harm to the body.

BAP1

BAP1 (BRACA-1 associated protein) is an important tumor-suppressing gene and protein in our body, its primary role is to help prevent cells from becoming cancerous. It helps control cell growth, cell division and cell death – like a quality control system.

In mesothelioma, loss or mutation of BAP1 can impair the cell’s ability to repair damaged DNA, allowing genetic mistakes to accumulate and abnormal cells to survive, increasing the risk of the development of cancer.

The loss of BAP1 can also cause an overexpression of another gene, EZH2. This genetic imbalance is part of the cellular mutation process that can result in the development of mesothelioma.

PD-L1

PD-L1 is a protein found on the surface of many cells, including cancer cells. The main role of PD-L1 is to regulate the immune system. It suppresses the body’s immune response by binding to PD-1 (programmed death-1) receptors on the immune system’s T cells. 

When the protein PD-L1 binds to PD-1 receptors, it sends a signal that turns off the activity of the T cells, preventing the immune system from recognizing cancer cells.

PD-L1 connects with the PD-1 receptors and deceives T-cells into believing mesothelioma cells are harmless. Many of the immunotherapy drugs used in the treatment of mesothelioma focus on blocking PD-L1 or PD-1, restoring T-cell’s ability to identify and attack cancer.

The U.S. Food and Drug Administration approved Opdivo, brand name nivolumab, for the treatment of mesothelioma. Opdivo is a PD-L1 inhibitor immunotherapy drug.

VISTA

VISTA is an immune system-suppressing protein. High levels of VISTA expression can subdue T-cells and prevent their attack against mesothelioma cells.

According to a study in Modern Pathology, VISTA was expressed in 85% of 319 analyzed mesothelioma cases. There are currently no VISTA targeting drugs approved by the FDA, but therapies are being studied in clinical studies – alone or in combination with other immunotherapy drugs.

CTLA-4 and B7

In mesothelioma, the CTLA-4 and B7 relation acts like a light switch, turning it on and off. B7 proteins help to activate T-cells while CTLA-4 acts like a brake. Cancer, like mesothelioma, can take advantage of this system.

B7 connects with the T-cell receptor CTLA-4. When binding occurs, the B7 protein inhibits the body’s immune system from responding to the presence of mesothelioma, allowing tumors to grow and spread.

The FDA approved Yervoy, brand name ipilimumab, for the treatment of mesothelioma. Yervoy is another checkpoint inhibitor drug, and works by blocking the attachment of B7 to CTLA-4, allowing the immune system to seek out and destroy mesothelioma cancer cells.

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Advancements in Gene Therapy for Mesothelioma

The role of genetics in mesothelioma treatment has become increasingly important as researchers learn more about the molecular changes that drive this disease. While treatment decisions are still largely based on factors such as cell type, stage, and overall health – genetic testing may provide doctors a way to identify patients who may benefit from targeted therapies.

Mesothelioma gene therapy has become one of the leading innovative treatments for mesothelioma. There are three different approaches being studied: therapies that block certain genes and proteins; therapies that use modified genes or viruses; and fixing damaged and mutated mesothelioma genes.

The targeted therapy tazemetostat is designed to block the protein EZH2 responsible for regulating cell growth. An overexpression of this protein is often found in mesothelioma. If EZH2 becomes overactive it can suppress genes that normally help prevent tumor growth. A recent phase 2 clinical trial testing tazemetostat resulted in a 64% response rate, meaning the treatment at least stalled the growth of their cancer.

TR002 is an investigative therapy that delivers the gene interferon alfa-2b directly into the cells lining the pleural cavity, where mesothelioma develops. Once in the cells, the gene stimulates the immune system to find and attack the cancer cells. The therapy showed a disease control rate of 87.5%.

Currently there is not a gene therapy proven capable of correcting damage or mutations found in mesothelioma tumors. Researchers are testing therapies designed to restore the function of damaged mesothelioma genes such as TP53 and CDKN2A, and they are exploring future approaches for BAP1 and CRISPR-based gene repair.

Gene Therapy Expert Joins Mesothelioma Guide Podcast

Dr. Daniel Sterman is the director of the Multidisciplinary Pulmonary Oncology Program at New York University Langone Health. He also led a progressed study that combines gene therapy and immunotherapy for pleural mesothelioma. Dr. Sterman joined the Mesothelioma Guide podcast to discuss the study and his efforts to advance gene therapy for mesothelioma.

“Many immunotherapies are drugs administered intravenously into the body,” Sterman said. “… There is a blockade in the tumor, and these drugs try to unleash that blockade.”

Half of the 300 enrollees received the experimental treatment: an adenovirus-delivered Interferon Alpha-2B along with chemotherapy (Gemcitabine) and an arthritis pain medication (Celecoxib). The other half received just the chemotherapy drug and pain medicine.

Sterman’s trial, he explained, involved a virus transporting a gene into the location of the mesothelioma. Once the gene reaches the site, the tumors produce interferon-alpha. The production of this causes an immune system reaction.

“We are injecting a cold virus into the chest cavity of patients with mesothelioma,” Sterman said. This cold virus has been modified so that it can’t replicate itself. It also can’t cause the common cold.”

Inhalable Gene Therapy for Mesothelioma and Lung Cancer

Researchers in Japan created an inhalable gene therapy: a combination of a gene therapy and inhalable powder. This unique therapy delivers the treatment into the lung cavity to fight cancer.

The tumor-suppressing gene drug, SFD-p16 and SFD-p53, targets three cell lines associated with the two cancers. Studies in mice showed the use of the inhalable gene therapy controlled cell growth and replication in these lines. The average volume of the tumors in these tests shrank thanks to the unique gene therapy.

p16 and p53 were the genes added. This inhalable gene therapy is another form of gene addition.

Accurate Prognosis with Gene Expression

Doctors can use gene expression analysis to estimate prognosis more accurately by identifying patterns of gene activity within a patient’s tumor. These tests examine tissue samples taken from a biopsy. Doctors can then cross-check the DNA from mesothelioma cells against healthy mesothelial cells and determine which genes are being expressed.

Doctors can predict the aggressiveness of a mesothelioma by studying the cells’ gene expression. For example, if a tumor-suppressing gene is damaged, this is a sign of a more aggressive disease.

Through the examination of gene expression doctors can also look for high levels of genes creating immune-suppressing proteins, like PD-L1 and B7. If doctors notice an abnormal amount of mesothelioma-related genes or proteins, they can utilize targeted checkpoint inhibitor drugs to activate or stimulate the immune system more effectively.

The benefits of gene expression analysis include:

• Ability to predict if a patient will benefit from surgery
• Determining the most appropriate targeted therapy
• Having a better understanding of how patients will tolerate chemotherapy and its effects
• Providing better prognostic accuracy

Gene expression tests help patients avoid undergoing unnecessary treatments. Having an accurate prognosis allows patients and families a greater sense of certainty and comfort in the treatment plan.

Mesothelioma specialists and researchers are constantly learning more about the disease at the genetic and molecular level. The best way patients can improve their prognosis is by seeing a specialist. Our team can help you connect with any of the top mesothelioma doctors in the country.

Sources & Author

1. Integrative Molecular Characterization of Malignant Pleural Mesothelioma. Cancer Discovery. Retrieved from: https://cancerdiscovery.aacrjournals.org/content/8/12/1548. Accessed: 06/11/2026.
2.  

   BAP1 gene. Genetics Home Reference. Retrieved from: https://ghr.nlm.nih.gov/gene/BAP1. Accessed: 06/11/2026.

3.  

   How do genes direct the production of proteins? Genetics Home Reference. Retrieved from: https://ghr.nlm.nih.gov/primer/howgeneswork/makingprotein. Accessed: 06/11/2026.

4.  

   V-domain Ig-containing suppressor of T-cell activation (VISTA), a potentially targetable immune checkpoint molecule, is highly expressed in epithelioid malignant pleural mesothelioma. Modern Pathology. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/31537897/. Accessed: 06/11/2026.

    

5. VISTA is an immune checkpoint molecule for human T cells. Cancer Research. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979527/. Accessed: 06/11/2026.

About the Writer, David Statman

David Statman is a Content Writer for Mesothelioma Guide. He received both his bachelor's and master's in journalism from West Virginia University, and has been in medical publishing since January 2022. He previously worked in sports journalism, primarily reporting on West Virginia sports for a number of publications.

He lives in Delaware with his wife, dog and two cats, and avidly competes as a professional wrestler in the Philadelphia area.