New Genetic Insights May Mean More Mesothelioma Treatment Options

Medical science has moved a step closer to better understanding the underlying genetic causes of malignant mesothelioma, a rare and hard-to-treat cancer.

The news, published in the journal Nature Genetics, means that some mesothelioma patients may benefit from drugs their physicians might not otherwise have thought to try.

Genetics and Mesothelioma

Like most cancers, pleural mesothelioma, a deadly malignancy caused primarily by asbestos exposure, has a genetic component.

Mesothelioma researchers around the world are working to identify the specific genetic alterations that cause certain cells in the membrane around the lungs to malfunction and replicate out of control.

Until the newly published study, several of these mutations had never been identified in malignant pleural mesothelioma.

A Spectrum of Mutations

Researchers at Brigham & Women’s Hospital in Boston and Genentech, Inc. in California, used advanced DNA sequencing technology to analyze samples of normal and malignant tissue from 216 patients with mesothelioma.

The tests identified a “spectrum of mutations” that may make certain people susceptible to mesothelioma, Fortunately, these same mutations may also make certain mesotheliomas susceptible to treatment with drugs that are currently used for other cancers.  

“A small number of these mutations have been found previously in other cancers, and drugs have been developed to target these mutations. No one knew before now that these mutations might also be found in mesothelioma tumors,” said co-author and Brigham and Women’s thoracic surgeon Raphael Bueno, MD, in a statement.

New Mesothelioma Treatment Options?

Currently, there are few treatment options for mesothelioma and even the drugs most commonly used to treat the disease have a limited success rate. The five-year survival rate for mesothelioma is less than 10 percent.

But the new research means that some mesothelioma patients who have not responded to treatment or who have relapsed after treatment could have some new options.

For example, more than a third of the mesothelioma tumors profiled by RNA sequencing were found to overexpress the PD-L1 immune checkpoint gene, potentially making them susceptible to immunotherapy. In other cases, genes were fused or missing.

A total of ten different genes were found to be “significantly mutated” in the malignant pleural mesothelioma samples.

The researchers suggest that mesothelioma outcomes may be improved in the future by performing genetic profiling on mesothelioma patients to determine their tumor’s unique “fingerprint” and match them with the most appropriate treatment.

Sources:

Bueno, R, et al, “Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations”, February 29, 2016, Nature Genetics

“New Genetic Insights Into Mesothelioma”, February 29, 2016, News Release, Brigham and Women’s Hospital website