Challenges of EGFR-TKIs in NSCLC and the potential role of herbs and active compounds: From mechanism to clinical practice

Abstract

Epidermal growth factor receptor (EGFR) mutations are the most common oncogenic driver in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are widely used in the treatment of lung cancer, especially in the first-line treatment of advanced NSCLC, and EGFR-TKIs monotherapy has achieved better efficacy and tolerability compared with standard chemotherapy. However, acquired resistance to EGFR-TKIs and associated adverse events pose a significant obstacle to targeted lung cancer therapy. Therefore, there is an urgent need to seek effective interventions to overcome these limitations. Natural medicines have shown potential therapeutic advantages in reversing acquired resistance to EGFR-TKIs and reducing adverse events, bringing new options and directions for EGFR-TKIs combination therapy. In this paper, we systematically demonstrated the resistance mechanism of EGFR-TKIs, the clinical strategy of each generation of EGFR-TKIs in the synergistic treatment of NSCLC, the treatment-related adverse events of EGFR-TKIs, and the potential role of traditional Chinese medicine in overcoming the resistance and adverse reactions of EGFR-TKIs. Herbs and active compounds have the potential to act synergistically through multiple pathways and multiple mechanisms of overall regulation, combined with targeted therapy, and are expected to be an innovative model for NSCLC treatment.

Nomogram-based prognostic tool for stage IIIB/IV non-small cell lung cancer patients undergoing traditional Chinese medicine treatment

“…TCM, characterized by its holistic approach, may exert multifaceted effects on cancer management, including the modulation of the immune system, inhibition of tumor growth, and an enhancement of the body's resilience against cancer-related fatigue and other side effects of conventional cancer therapies [ 22 ]. The synergistic interaction between TCM and targeted therapies, such as EGFR-TKIs, could potentially amplify therapeutic efficacy, thereby extending PFS and OS [ 23 , 24 ]. Furthermore, the phytochemical constituents of various TCM formulations may exert anticancer effects through multiple pathways, such as apoptosis induction, angiogenesis inhibition, and metastasis suppression [ 25 , 26 ].…”