In a recent study, researchers have uncovered the biological trigger behind the dangerous immune-related adverse events (irAEs) that occur when the epidermal growth factor receptor (EGFR) inhibitor osimertinib is combined with immune checkpoint inhibitors (ICIs). Using a preclinical mouse model, the team found that this drug duo activates the IL-6/JAK/STAT3 signaling pathway in liver macrophages, unleashing a cytokine storm-like inflammatory response. Importantly, the addition of the JAK inhibitor ruxolitinib successfully dampened this response, significantly lowering levels of key inflammatory markers in the bloodstream. These findings point to a viable path forward in reducing the life-threatening toxicity associated with combination cancer therapies.
