JAK inhibitors alleviate EGFR-inhibitor-induced diarrhoea by protecting intestinal stem cells from adaptive-immune-exacerbated injury

Epidermal growth factor receptor (EGFR) inhibitors (EGFRi) are a milestone in targeted cancer therapy, with tyrosine kinase inhibitors (TKIs) such as afatinib showing strong efficacy in non-small cell lung cancer and other solid tumors. However, their clinical utility is frequently limited by gastrointestinal toxicity-particularly severe diarrhea, affecting up to 75% of patients-which often leads to treatment interruption or dose reduction and compromises antitumor benefit. Current management relies mainly on empirical symptomatic care and lacks mechanistic, targeted interventions. Understanding the pathogenic basis of EGFRi-induced intestinal injury is therefore urgently needed.