Investigators at Mass General Brigham have uncovered how resistance to chemotherapies may occur in some cancers. Researchers focused on a pathway that harnesses reactive oxygen species (ROS) to kill cancer cells. The study found that mutations to VPS35, a key player in this pathway, can prevent chemotherapy-induced cell death. These results, published in Nature, could help pinpoint treatment-resistant tumors.

“ROS play an important role in healthy and diseased cells, but pathways that sense and control cellular ROS levels are not well understood,” said corresponding author Liron Bar-Peled, Ph.D., of the Krantz Family Center for Cancer Research at Mass General Cancer Center (MGCC), a member of the Mass General Brigham health care system. “A clearer understanding of ROS could help us understand why chemoresistance occurs in some cases.”

Low concentrations of ROS are required for normal cell signaling, but higher levels of ROS can damage cells and contribute to diseases such as cancer and neurodegeneration. Researchers know that mitochondria play an important role in ROS production, but it has been unclear if ROS-sensing proteins influence the mitochondria. If they do, this could impact responses to some anti-cancer treatments.