Abstract
Conventional treatments, including chemotherapy, immunotherapy, targeted therapy and radiotherapy, are effective clinical strategies for non-small cell lung cancer (NSCLC) patients, which can significantly improve life quality and prolong survival time. However, the application of drugs in NSCLC patients inevitably leads to therapeutic resistance. In recent years, many studies have shown that histone methyltransferases (HMTs), including both protein arginine methyltransferases (PRMTs) and lysine methyltransferases (KMTs), play pivotal roles in tumor initiation, progression, and treatment resistance. This review synthesizes current insights into histone methylation dynamics driving therapeutic resistance, with a focus on key HMTs and their mechanisms. Additionally, we discuss the molecular mechanisms underlying histone methylation-mediated therapeutic resistance and potential therapeutic strategies targeting histone methylation for overcoming therapeutic resistance in NSCLC.