Researchers at the Memorial Sloan Kettering (MSK) Cancer Center in New York City have been working diligently to find a promising treatment for mesothelioma — and it looks like their hard work may finally be paying off. Last week, the group announced that their research into BRCA1 associated protein-1 (BAP1) mutations could ultimately help nearly 50% of all mesothelioma patients. With around 3,200 new cases of mesothelioma in the U.S., each year, this discovery could prove itself a tremendous impact.
Mesothelioma and BAP1 Mutations
Mesothelioma is a rare cancer caused directly by exposure to asbestos. However, not everyone who inhales asbestos fibers will develop mesothelioma – and that’s where the BAP1 gene comes in to play. BAP1 is a human gene, and it can act as a tumor suppressor; it might also be involved in regulation of cell growth. When the gene mutates, its mutation could be associated with an increased risk of a few different rare cancers.
In 2011, researchers found that individuals with BAP1 mutations were at a higher risk of developing malignant mesothelioma. Marc Ladanyi, the experimental pathologist at MSK who made this discovery, noted that while a small number of mesothelioma patients inherited the BAP1 mutation from their parents, about 50 to 60% of all mesothelioma tumors have BAP1 mutations.
Before the drug bevacizumab (Avastin) was found to improve the survival rate for mesothelioma patients this year, there hadn’t been a new drug to treat malignant mesothelioma for over a decade. However, with MSK’s recent breakthrough, researchers see promise in drug trials that block an enzyme called EZH2, which is linked to BAP1 mutations.
EZH2 Inhibitors: Blocking Mesothelioma Tumor Growth
Drugs called EZH2 inhibitors are already in developmental stages and some have even completed early-stage trials that show they are safe to use in certain patients. These drugs may be useful with BAP1 mutations because researchers found that when the BAP1 gene becomes inactive (due to mutations), the levels of EZH2 go up and mesothelioma cells can grow rapidly.
“When BAP1 is knocked out and EZH2 levels goes up, it leads to inappropriate modification of a particular histone, which is the mechanism by which cells are able to proliferate out of control,” said physician-scientist Scott Armstrong, head of MSK’s Center for Epigenetics Research.
What Does This Mean for Mesothelioma Patients?
In an article about their findings, MSK said their investigators are figuring out next steps. They would like to extend their laboratory observations to the clinic, and they are also working with Epizyme, a biotechnology firm, to study EZH2 inhibitors in mesothelioma patients.
For mesothelioma patients, this calls attention to the important role genetics can play in causing this deadly form of cancer to develop. Victims cannot go back in time and stop their exposure to asbestos, but if doctors know about an individual’s BAP1 mutation, they may have the ability to stop mesothelioma before it even starts, or to shut it down in the early stages.
While current mesothelioma treatment will not be directly and immediately affected, there could be big changes in the future if a safe drug is developed and approved. Being able to link about half of mesothelioma cases to BAP1 mutations — and controlling levels of EZH2 — means that potentially, a new drug developed from the results of these findings could save thousands of lives.