Study Highlights How Genes Impact Mesothelioma Survival

A new National Cancer Institute study shines a light on some of the ways genes impact mesothelioma survival. It could have important implications for mesothelioma treatment.

The study was led by prominent mesothelioma researcher Raffit Hassan, MD. It focused on genetic mutations that may make certain mesothelioma patients more sensitive to chemotherapy.

Genes, Genotype, and Mesothelioma Treatment

A mesothelioma patient’s unique collection of genes, including genetic mutations, is known as their genotype.

Genes impact mesothelioma survival in a variety of ways. Tumor suppressor genes are supposed to help keep tumors from forming. People with mutations on these genes may be more likely to get malignant mesothelioma.

Other genes influence the cancer’s ability to “hide” from detection by the immune system. Some new treatments for mesothelioma focus on trying to offset the effects of these mutations.

DNA Repair Genes Impact Mesothelioma Survival

In the current mesothelioma study, Dr. Hassan and his colleagues analyzed how DNA repair genes impact mesothelioma survival.

DNA repair genes are supposed to help fix problems that can naturally crop up in the DNA during a cell’s life. Part of their job is to help keep tumors from forming in the first place.

But the new study shows that mesothelioma patients with mutations in these genes may also be more susceptible to chemotherapy. When chemotherapy damages DNA in these patients’ mesothelioma cells, the cells may not be able to recover.

As a result, it appears that these genes impact mesothelioma survival positively.

“Among 385 patients treated with platinum chemotherapy, median overall survival was significantly longer for patients with loss-of-function mutations in any of the targeted genes compared with patients with no such mutation,” writes Dr. Hassan.

The Effect of Genotype on Mesothelioma Prognosis

Apparently genes impact mesothelioma survival differently depending on what type of mesothelioma a patient has.

The study found that pleural mesothelioma patients with loss-of-function genetic mutations who had chemotherapy had a median survival of 7.9 years versus 2.4 year. Pleural mesothelioma affects the lining around the lungs. It is the most common type.

In contrast, There was no significant survival difference in peritoneal mesothelioma patients with or without these same loss-of-function mutations. Peritoneal mesothelioma impacts the lining around the abdomen. About a fifth of mesothelioma cases are this kind.

The researchers conclude: “Patients with pleural mesothelioma with inherited mutations in DNA repair and other tumor suppressor genes appear to particularly benefit from platinum chemotherapy compared with patients without inherited mutations.”

In general, chemotherapy for mesothelioma is only moderately effective. It typically extends survival by only a few months. Knowing ahead of time which patients are most likely to benefit could help in treatment planning.

Source:

Hassan, R, et al, “Inherited predisposition to malignant mesothelioma and overall survival following platinum chemotherapy”, April 11, 2019, Proc Natl Acad Sci USA, Epub ahead of print, https://www.pnas.org/content/early/2019/04/10/1821510116