Hawaii Identifies L-BAM, Treatable Mesothelioma
UH Cancer Center researchers discover a genetic mesothelioma variant caused by BAP1 mutations, not asbestos, that responds to standard treatment.
Researchers at the University of Hawaii Cancer Center have identified a distinct, treatable form of mesothelioma driven by inherited genetic mutations rather than asbestos exposure. The variant, called low-grade BAP1-associated mesothelioma (L-BAM), responds to standard cancer therapies and can allow near-normal lifespans when detected early.
The findings appeared in the Journal of Thoracic Oncology (Volume 20, Issue 11, November 2025; first posted online June 27, 2025) and were presented at the IASLC World Conference on Lung Cancer in Barcelona on September 6, 2025. The University of Hawaii Cancer Center announced the work on September 30, 2025.
A Different Disease Entirely
Mesothelioma caused by asbestos exposure is aggressive and resistant to most treatments, with a median survival of six to 18 months. L-BAM is biologically distinct. It arises from inherited germline mutations in the BAP1 tumor suppressor gene and follows a far less aggressive course.
The research team, led by Drs. Michele Carbone and Haining Yang, studied families across Louisiana, Wisconsin, and Turkey before expanding to diverse populations including Native Hawaiian, Japanese, and Jewish communities. They found that L-BAM patients who received standard treatments, including surgery and chemotherapy, could achieve outcomes dramatically better than those with the asbestos-related form.
“This is not the same disease,” the researchers concluded. Where asbestos-related mesothelioma has been described as “uniformly lethal,” L-BAM is manageable with existing therapies.
Why It Matters
Approximately 3,000 people are diagnosed with mesothelioma in the United States each year, with roughly 2,500 deaths. The vast majority of cases are linked to asbestos. But a subset of patients, particularly those with no known asbestos exposure, may carry BAP1 mutations that place them in the L-BAM category.
For these patients, the distinction is life-changing. Rather than facing a prognosis measured in months, early detection through genetic testing can lead to treatment plans that extend survival significantly.
The discovery also carries implications for cancer screening more broadly. People with BAP1 mutations face elevated risks of multiple cancer types beyond mesothelioma, including melanoma, kidney cancer, breast cancer, and liver cancer. Identifying carriers early allows physicians to monitor for these associated cancers before they progress.
Genetic Testing Is Available Now
BAP1 genetic testing is currently available in the United States and abroad. The UH Cancer Center recommends testing for anyone diagnosed with mesothelioma who has no clear asbestos exposure history, as well as family members of known BAP1 mutation carriers.
The test can distinguish L-BAM from asbestos-related mesothelioma, allowing physicians to tailor treatment accordingly. For families with a history of mesothelioma or the associated cancer types, genetic counseling can identify at-risk individuals before symptoms develop.
BAP1 genetic testing is available through major cancer centers and genetic testing services. People diagnosed with mesothelioma without a clear asbestos exposure history, or those with family histories of mesothelioma, melanoma, or kidney cancer, may benefit from testing.
What Comes Next
The findings have been validated in collaboration with the National Cancer Institute and presented at major institutions including MD Anderson, Memorial Sloan Kettering, and NCI. Ongoing research funded by an NCI R01 grant continues to explore personalized treatment approaches for BAP1-mutated cancers.
Several experimental therapies currently in clinical trials may prove particularly effective for L-BAM patients. These include Hippo/TEAD pathway inhibitors like VT3989 and arginine-depleting agents like pegargiminase, both of which target molecular pathways relevant to BAP1-mutated tumors.
For a disease where prognosis has historically been measured in months, the identification of a treatable variant represents a meaningful advance. The key is getting the right diagnosis through genetic testing, so patients receive the treatment approach that matches their specific form of the disease.
References
University of Hawaii News. (2025-09-30). UH Cancer Center identifies treatable form of mesothelioma.
https://www.hawaii.edu/news/2025/09/30/treatable-mesothelioma-variant/
UH Cancer Center. (2025-10-01). UH Cancer Center Identifies Treatable Form of Mesothelioma.
https://www.uhcancercenter.org/news/press-releases/uh-cancer-center-identifies-treatable-form-of-mesothelioma
Reader Q&A
Frequently Asked Questions
What is L-BAM mesothelioma?
Who should get BAP1 genetic testing?
What other cancers are associated with BAP1 mutations?
How did Steve McQueen get mesothelioma?
Steve McQueen was exposed to asbestos through multiple occupational and military sources over several decades. His primary exposure occurred during his service in the U.S. Marine Corps from 1947 to 1950, when he worked aboard naval ships and in shipyards, including removing asbestos lagging from pipes at Camp Lejeune. After his military service, he encountered additional asbestos exposure on movie soundstages where insulation contained the mineral, while wearing flame-resistant racing suits made with asbestos, and while working on race car and motorcycle brakes. McQueen did not develop symptoms until 1978, nearly 30 years after his initial military exposure, reflecting the typical latency period of 20 to 50 years between asbestos exposure and mesothelioma diagnosis. He was diagnosed with pleural mesothelioma in December 1979 and died in November 1980 at age 50.
How long can you live with stage 1 mesothelioma?
People with stage 1 pleural mesothelioma have a median survival of 19 to 22 months with treatment, according to data from the National Cancer Database and International Association for the Study of Lung Cancer. A Frontiers in Oncology report cites an average life expectancy of 21 months for stage 1. The 5-year survival rate ranges from 11% to 23% depending on treatment and tumor location, with higher rates reported for peritoneal cases at 87%.
What to do if you have the BAP1 mutation?
People with an inherited BAP1 mutation face higher risks of mesothelioma, uveal melanoma, and other cancers, which may show variable aggressiveness and treatment responses depending on the tumor type. Studies indicate BAP1-mutated mesothelioma tumors can respond to PARP inhibitors, EZH2 inhibitors like tazemetostat (tested in phase 2 trials for relapsed cases), and immunotherapies such as pembrolizumab, with preclinical data showing tumor shrinkage from certain drug combinations. No specific treatments are approved solely for BAP1 mutations, and clinical trial outcomes remain mixed, with ongoing research into HDAC inhibitors like vorinostat and other pathway-targeted agents. Genetic testing and tumor profiling guide prognosis, as BAP1 alterations correlate with longer survival in some mesothelioma cases when targeted appropriately.
How rare is BAP1?
BAP1 tumor predisposition syndrome, caused by germline BAP1 mutations, is rare, with more than 70 families described in medical literature. Only 1% of mesotheliomas are attributed to germline BAP1 mutations, though people with these mutations have a 15-25% lifetime risk of mesothelioma versus less than 1% in the general population. Pathogenic BAP1 mutations occur in 1.3% of tumors across 20 cancer types, with higher rates in uveal melanoma (50%) and malignant pleural mesothelioma (29%). Inherited BAP1 mutations are very rare even among melanoma patients.