Of particular relevance to GBM therapy, high CcO activity supports more efficient mitochondrial coupling and thus decreased the production of reactive oxygen species (ROS),8–11 thereby diminishing the efficacy of chemotherapeutic drugs such as TMZ.12,13 In our previous retrospective study, high CcO activity was correlated with poor overall survival (OS) and progression-free survival (PFS).14 A receiver-operating characteristic (ROC) analysis in that study determined that a CcO/citrate synthase (CS) ratio of 4 was the optimal cutoff value. The gene discussed is RYR1; the disease is glioblastoma.