Scientists at Mass General Brigham have made significant strides in understanding why some cancers develop resistance to chemotherapy. Their research delves into a biological pathway that leverages reactive oxygen species (ROS) for eliminating cancer cells. The findings indicate that mutations in VPS35, an essential component of this mechanism, can inhibit chemotherapy-induced cell death. Published in Nature, these results may pave the way for identifying tumors resistant to treatment, offering hope for more targeted therapies.

Reactive oxygen species are crucial elements in both normal and pathological cellular processes. However, the pathways responsible for detecting and regulating ROS levels within cells remain largely unknown. Dr. Liron Bar-Peled from the Krantz Family Center for Cancer Research highlights that comprehending ROS could elucidate the reasons behind chemotherapy resistance in certain cases. While low ROS concentrations support regular cell communication, excessive amounts can lead to cellular damage, contributing to diseases like cancer and neurodegeneration.

Research indicates that mitochondria significantly influence ROS production, yet whether ROS-sensing proteins impact mitochondrial function remains unclear. This uncertainty prompted a team led by Drs. Junbing Zhang, Yousuf Ali, and Harrison Chong to screen cancer cells for proteins linked to chemoresistance. Their investigation uncovered mutations associated with increased treatment resistance, tracing two such mutations to the protein VPS35. Further studies revealed that these mutations result in reduced intracellular ROS levels.

In a related study, researchers examined VPS35 expression levels in 24 patients with high-grade serous ovarian cancer who underwent treatment at the Mass General Cancer Center. They discovered that higher VPS35 levels in tumors correlated with better treatment outcomes and improved overall survival rates.

This groundbreaking research underscores the importance of understanding ROS pathways and their role in chemotherapy resistance. By pinpointing specific mutations and proteins involved in this process, scientists may be able to design more effective treatments tailored to individual patient needs, potentially revolutionizing cancer care strategies.