Genetic mutation diminishes drug response in some cancer patients

Researchers at Boston-based Mass General Brigham have discovered a key mutation that may be a driving factor in resistance to certain drugs used to treat breast cancer patients, according to a Nov. 2 news release. 

A drug given to treat patients with certain types of cancer, like breast cancer, known as Alpelisib, which is a PI3Kα inhibitor. But if an individual has a cancer with a mutated version of the PIK3CA gene, they develop resistance to the drug. 

Mass General researchers found that sometimes, resistance may also be caused by "secondary mutations in the PIK3CA gene itself," which can lead to a reduction in drug binding. 

However, they note that a new class of PI3Kα inhibitors could be a more effective therapy for individuals with the mutation, but questions still remain, and more research is needed, the study's lead authors underscored.

"As more and more patients are treated with PI3Kα inhibitors, we are studying how frequent each of these acquired genomic alterations are," said Dejan Juric, MD, co-lead on the study and director of the Termeer Center for Targeted Therapies & Investigational Cancer Therapeutics Program at the Mass General Cancer Center. "Moreover, a significant portion of our patients do not present any of these mutations at the time of disease progression, indicating that the puzzle is far from being completed."

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