Though malignant mesothelioma is a uniquely challenging form of cancer, it shares many traits with other cancers that scientists are investigating as therapeutic targets. Among these is a mutation of PI3K-AKT-mTOR, a pathway that controls metabolism. When this mutation is present it protects cancerous cells, but researchers from Memorial Sloan Kettering Cancer Center in New York believe they’ve found a way to block this effect, creating a potent and effective way of killing cancerous tumors.
Sabotaging Mutation May Present Key to Mesothelioma Tumor Death
The new research is focused on ferroptosis, a type of cell death triggered by oxidative stress that mesothelioma and other types of cancers appear immune to. Normally, free radicals and chemicals accumulate in cells as they use oxygen to burn fuel for energy, and these byproducts – including iron — end up killing the cell. But mutations in the PI3K-AKT-mTOR pathway protect against this stress.
According to a study published in Proceedings of the National Academy of Sciences (PNAS) by Xuejun Jiang, a cell biologist in the Sloan Kettering Institute, and Craig Thompson, President and CEO of Memorial Sloan Kettering, by blocking the effects of this stress while at the same time providing a drug that promotes ferroptosis, they were able to achieve remarkable outcomes.
Mutation Common to Many Forms of Cancer
Though the researchers tested their approach on breast and prostate cancers in lab animals, the PI3K-AKT-mTOR mutation is found in many types of resistant cancers, including malignant mesothelioma. All of these cancer types have previously demonstrated significant resistance to a drug that induces ferroptosis, but the researchers found that when they were also given a drug that blocked the metabolic pathway, they achieved near destruction of the tumors.
Speaking of their results, Dr. Jiang said, “These were some of the most significant tumor regressions I’ve ever seen coming from experiments in my lab.” Further exploration revealed the mechanism of the mutation. The team learned that PI3K-AKT-mTOR boosts the presence of lipids in the cancer cell’s outer membrane that protect against the oxidative stress. By blocking the mutation, they were able to stop this protective coating from forming. The researchers plan to begin testing their approach on other types of cancer.
If you or someone you love has been diagnosed with malignant mesothelioma, research like this offers tremendous promise. For information on other innovations, contact the Patient Advocates at Mesothelioma.net at 1-800-692-8608.
