New Discoveries on Genetic Mutations Linked to Chemotherapy Resistance

Recent research conducted by scientists at Mass General Brigham has revealed important insights into how certain cancers may develop resistance to chemotherapy treatments. The team focused on a specific biological pathway that utilizes reactive oxygen species (ROS) to induce cell death in cancer cells. Their findings, published in the prestigious journal Nature, highlight mutations in the VPS35 gene as a critical factor that can hinder the effectiveness of chemotherapy.

According to the researchers, understanding the role of ROS is essential, as these molecules are crucial for both healthy and diseased cells. Liron Bar-Peled, Ph.D., from the Krantz Family Center for Cancer Research, emphasized that while ROS are vital for normal cellular signaling, excessive levels can damage cells and contribute to various diseases, including cancer and neurodegeneration. The research aims to shed light on the mechanisms behind chemotherapy resistance, a significant hurdle in cancer treatment.

In their investigation, the research team, led by co-first authors Junbing Zhang, Ph.D., Yousuf Ali, Ph.D., and Harrison Chong, conducted a screening of cancer cells to identify ROS-sensing proteins that might contribute to resistance against chemotherapy. The study identified specific mutations that were linked to increased resistance to treatment, particularly mutations related to the VPS35 protein. Subsequent analysis revealed that these mutations resulted in reduced levels of ROS within the cancer cells.

The researchers also evaluated VPS35 expression in a cohort of 24 patients diagnosed with high-grade serous ovarian cancer (HGSOC) who were treated at Mass General Brigham. Their observations indicated that higher levels of VPS35 in tumors correlated with better responses to chemotherapy and improved overall survival rates for the patients.

This research provides a deeper understanding of the genetic factors contributing to chemotherapy resistance, offering potential avenues for developing more effective treatment strategies. By identifying the role of VPS35 and its mutations, healthcare professionals may be able to better predict which tumors are likely to resist standard chemotherapy treatments, paving the way for personalized cancer therapies that could enhance patient outcomes.

For further details, the complete study can be accessed in Nature under the title: Oxidation of retromer complex controls mitochondrial translation.