Different Mesothelioma Subtypes: Gene Study Could Lead to Targeted Treatments

A group of European pathologists say the different mesothelioma subtypes have significant differences in their pattern of gene expression. Exploiting these differences could help scientists craft more effective mesothelioma treatments. 

Asbestos exposure is the primary cause of mesothelioma. But doctors know that genetics play a role, too. Newly-approved immunotherapy drugs target proteins expressed by specific genes. But these drugs work much better in some mesothelioma patients than they do in others. 

The new study suggests that differences in the genetic profiles of different mesothelioma subtypes could help explain why. 

Immunotherapy Drugs for Mesothelioma

Immunotherapy is an up-and-coming treatment approach for mesothelioma and other cancers. It harnesses the power of the person’s immune system to fight cancer. 

In people with mesothelioma, genes that are supposed to help the body prevent or fight cancer may be mutated or missing. Immunotherapy drugs aim to activate cancer-fighting genes and turn off cancer-promoting genes. 

But it turns out that different mesothelioma subtypes have different genetic profiles. These differences may impact how well they respond to immunotherapy. 

The FDA recently approved the immunotherapy drugs Yervoy (ipilimumab) and Opdivo (nivolumab) for mesothelioma. But doctors are still trying to understand which patients are most likely to benefit from these drugs. It is important to pick the right treatment as early as possible because mesothelioma tumors grow and spread so quickly.

Genetic Profiles of Different Mesothelioma Subtypes

The new study involved pathologists at university hospitals in Austria and Germany. They examined pleural mesothelioma tumor samples from 22 patients who died. The two different mesothelioma subtypes represented in the samples were sarcomatoid (12) and epithelioid (10).

The researchers isolated the RNA of these samples and ran it through a digital gene expression pattern analysis. 

“Our study revealed a notable difference between epithelioid and sarcomatoid mesothelioma, showing differential gene expression for 304/698 expressed genes,” writes lead author Luka Brcic of Austria’s Medical University of Graz. 

Some differences between the different mesothelioma subtypes are subtle but important. Understanding them could mean the difference between a mesothelioma treatment that works and one that has no effect. 

“Our work reveals the specific role of the immune system within the different histologic subtypes of malignant pleural mesothelioma, providing a more detailed background of their immunogenic potential,” writes Dr. Brcic.

The study highlights the fact that there is no one-size-fits-all treatment for mesothelioma. It is important for patients to work closely with their doctors to understand their specific case. Getting involved in a clinical trial is one of the best ways to access promising new mesothelioma treatments. Visit ClinicalTrials.gov for a list of open studies and eligibility criteria. 

Sources:

Brcic, L, et al, “Digital Gene Expression Analysis of Epithelioid and Sarcomatoid Mesothelioma Reveals Differences in Immunogenicity”, April 7, 2021, Cancers, Open access article, https://www.mdpi.com/2072-6694/13/8/1761