Mesothelioma is an extremely challenging form of cancer. The rare, asbestos-related disease only has a 10% five-year survival rate, but a new study published by researchers from The First Affiliated Hospital of Nanjing Medical University in Nanjing, China, has offered a promising new treatment approach.
Scientists Discover a Genetic Weakness in Mesothelioma
In a report recently published in the scientific journal EMBO Molecular Medicine, a research team led by Duo Xu of the hospital’s Department of Oncology discovered that NF2-deficient mesothelioma cells become “addicted” to producing pyrimidines through a specific pathway. Pyrimidines are molecules that all cells need to make DNA and reproduce. The production of these crucial building blocks is boosted by two key enzymes – CAD and DHODH. This creates a vulnerability that scientists hope to take advantage of: If this production line can be blocked, the cancer cells can’t survive.
The scientists’ investigation was driven by the knowledge that roughly one-third of all mesothelioma cases have mutations in a gene called NF2 (neurofibromatosis 2). Normally, NF2 stops cell growth, but when its mechanism is broken in mesothelioma cells, a protein called YAP becomes overactive. This overactive protein has a profound effect on patient health, driving cancer cells to grow rapidly while consuming massive amounts of pyrimidines in a sort of metabolic addiction.
Targeting Mesothelioma’s Pyrimidine Addiction
The Chinese researchers found that specific drugs called DHODH inhibitors can effectively starve NF2-altered mesothelioma cells by blocking their ability to make pyrimidines. One of these drugs, leflunomide, has already been approved by the FDA for other conditions and has a good safety record. Another drug, brequinar, showed even stronger effects when combined with the chemotherapy drug cisplatin. In laboratory and animal studies, this combination approach significantly improved patients’ outcomes.
With roughly half of all mesothelioma patients having the genetic profile that would make them candidates for this targeted therapy, there is new hope for patients with this notoriously difficult form of cancer. The discovery represents a major advance in precision medicine for the treatment of asbestos-related disease, as, instead of offering a one-size-fits-all approach, it has the potential to allow doctors to test tumors for NF2 mutations and, if patients test positive, to specifically treat them with DHODH inhibitors.
While groundbreaking research offers real hope for patients diagnosed with mesothelioma, the Patient Advocates at Mesothelioma.net can offer assistance and support in other important ways. For more information, contact us today at 1-800-692-8608.
