Scientists have discovered a promising drug combination that shrinks tumors and prolongs survival in patients with mesothelioma and other cancers that contain BAP1 mutations. The treatment approach takes advantage of the fact that the genetic change makes the asbestos-related cancer’s deadly tumors less aggressive and more treatable than those without the mutation.
Mesothelioma Patients with BAP1 Mutations Show Dramatically Better Survival
The study, published in Science Translational Medicine, examined the BAP1 gene and its role in DNA repair pathways. Researchers found that when BAP1 is missing or damaged in mesothelioma and other cancer cells, which is what characterizes the BAP1 mutation, it blocks two specific proteins—LSD1 and PARP1. This disrupts the cancer cell’s ability to maintain its DNA, causing the tumor cells to die.
“BAP1 mutations are relatively common across several aggressive cancers, but there are still limited targeted treatment options for these patients,” explained Dr. Bin Tean Teh, a clinician-scientist at Duke-NUS Medical School and National Cancer Center Singapore who led the study. “That gap between biological importance and clinical translation was a key motivation for us.”
Mesothelioma Drug Combination Shows Promise in Multiple Cancer Types
The mesothelioma treatment research revealed that BAP1 acts as a protective enzyme, helping shield other proteins from being broken down by the cell’s waste disposal system. When researchers characterized BAP1’s activity, they discovered it plays a role in a DNA maintenance pathway that keeps genetic material healthy.
Based on this finding, the Duke researchers tested tumors from mesothelioma patients, engrafting them onto mice and treating them with two inhibiting compounds at the same time. In the animals implanted with the mesothelioma cells, the combination therapy shrank tumors and improved survival.
“Our findings suggest that BAP1 contributes to maintaining genome integrity, in part by regulating proteins involved in DNA damage recognition,” said the study’s lead author, Dr. Jing Han Hong. When mesothelioma tumors lose BAP1 function, the genome becomes destabilized—but this vulnerability can be exploited with targeted drug combinations. Additionally, the fact that both mesothelioma treatment inhibitors have already been tested in humans should make clinical trials straightforward.
BAP1 Mutation in Mesothelioma Provides Better Prognosis With Appropriate Treatment
According to Michele Carbone, M.D., Ph.D., an oncologist at the University of Hawaiʻi Cancer Center who was not involved with the new study, “Mesothelioma in a carrier of BAP1 mutation in the germline is a different disease.” He says that mesothelioma patients with inherited BAP1 mutations survive seven times longer than those without the mutation. This survival advantage suggests that BAP1 mutations create tumors that are less invasive, easier to treat, and associated with dramatically better patient outcomes—making the discovery of targeted therapies for BAP1-deficient cancers particularly promising.
If you or someone you love has been diagnosed with mesothelioma, discoveries like these offer real promise. For more information and access to helpful resources, contact the Patient Advocates at Mesothelioma.net today at 1-800-692-8608.
