Malignant Pleural Mesothelioma Study Finds Genetic Alterations in Tumors, Some with Possibility of Treatment

Malignant Pleural Mesothelioma Study Finds Genetic Alterations in Tumors, Some with Possibility of Treatment

Researchers involved in the International Mesothelioma Program at Brigham and Women’s Hospital (BWH), working with scientists at Genentech, analyzed hundreds of malignant pleural mesothelioma tumors and, through genomic analyses, found a series of previously unknown genetic alterations. The mutated genes included some previously found in other cancers, having approved treatments available, as well as others that may improve the diagnostics, survival prognostics, and screening of mesothelioma.

Their study, titled “Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations,” was published in the journal Nature Genetics.

Physician-scientists at the International Mesothelioma Program at BWH, one of the largest mesothelioma treatment and research programs in the world, provide care for patients while also studying the disease’s biology and possible new therapeutic strategies.

The research team analyzed 216 malignant pleural mesothelioma (MPM) samples regarding DNA and RNA profiles. Through this large-scale genomic analysis, researchers uncovered more than 2,500 genetic alterations and identified 10 significantly mutated genes. Some of these genetic alterations suggested that targeted therapies, such as the BCR-ABL-1 inhibitor, could be matched to a patient’s tumor. Moreover, the scientists found that a specific subtype of mesothelioma, sarcomatoid, might be a good candidate for anti-PD-L1 therapy.

“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 the study’s lead author, Raphael Bueno, MD, chief of the Division of Thoracic Surgery at BWH and co-director of the BWH Lung Center, in a news release. “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.”

Mesothelioma is a rare but deadly cancer whose incidence has grown in the last decades, mainly due to past exposure to asbestos, one of its main risk factors. This type of cancer affects the mesothelial cells, which form a thin layer that covers, protects, and lubricates serous cavities, consisting of the membranes pleura (in the lungs), pericardium (heart), and peritoneum (abdomen), as well as the surfaces of internal organs. Diagnosis of mesothelioma usually occurs in an advanced stage of the disease, a factor that greatly contributes to its low overall survival. According to the Mesothelioma Cancer Alliance, only 5 percent to 10 percent of mesothelioma patients live at least five years after diagnosis.

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