Mesothelioma is a rare but deadly form of cancer that is caused by exposure to asbestos. With symptoms not usually present until twenty to forty years after exposure to asbestos, available treatment for this disease offers very little help, especially for patients who are in the final stages of mesothelioma.
In a comprehensive genomic analysis using over 200 tumors, researchers from Brigham and Women’s Hospital and scientists from Genentech have discovered previously unknown genetic alterations, including some that may be clinically actionable, as well as others which may improve diagnostics, screenings, and predictions about outcomes for patients.
Researchers analysed 216 malignant pleural mesothelioma (MPM) samples, comparing DNA and RNA from normal tissue to cancerous tissue. The team found over 2,500 alterations and identified 10 significantly mutated genes. They also discovered the presence of immune cells at the site of the tumor.
Some of the alterations they discovered suggest that available targeted therapies could be matched to a patient’s tumor. Other alterations and the presence of immune targets could serve as better markers to help physicians more accurately diagnose mesothelioma and predict which patients will have better or poor outcomes.
“By studying so many samples, we’ve been able to describe a spectrum of mutations for this rare disease,” said lead author, Raphael Bueno, MD, chief of the Division of Thoracic Surgery at BWH and co-director of the BWH Lung Center.
“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. This new work suggests that patients with such mutations may benefit from certain existing drugs,” he said.
According to the American Cancer Society, there are about 3,000 new cases being diagnosed yearly. Mesothelioma is more common among older people than younger people.
“When you have a cancer that has a 80 to 90 percent mortality rate within five years of diagnosis, and you discover evidence that a small percentage of people may have actionable mutations, that means that you could reduce mortality,” said Dr. Bueno. “Even for a mutation that happens one to two percent of the time, it could mean the difference between life and death for a patient. We plan to continue this important research through investigator-sponsored trials evaluating the potential use of cancer immunotherapies for the treatment of mesothelioma.”
The study has been published in Nature Genetics and was funded by donations to the International Mesothelioma Program, industry grants from Genentech and grants from the National Cancer Institute.