School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
Zhejiang Institute for Food and Drug Control, NMPA Key Laboratory for Quality Evaluation of Traditional Chinese Medicine, Hangzhou, 310052, China.
Eur J Pharmacol. 2024 Oct 5;980:176871. doi: 10.1016/j.ejphar.2024.176871. Epub 2024 Aug 6.
Non-small cell lung cancer (NSCLC) poses a global health threat, and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib, afatinib, and osimertinib have achieved significant success in clinical treatment. However, the emergence of resistance limits the long-term efficacy of these treatments, necessitating urgent exploration of novel EGFR-TKIs. This review provides an in-depth summary and exploration of the resistance mechanisms associated with EGFR-TKIs, with a specific focus on representative drugs like gefitinib, afatinib, and osimertinib. Additionally, the review introduces a therapeutic strategy involving the combination of Chinese herbal medicines (CHMs) and chemotherapy drugs, highlighting the potential role of CHMs in overcoming NSCLC resistance. Through systematic analysis, we elucidate the primary resistance mechanisms of EGFR-TKIs in NSCLC treatment, emphasizing CHMs as potential treatment medicines and providing a fresh perspective for the development of next-generation EGFR-TKIs. This comprehensive review aims to guide the application of CHMs in combination therapy for NSCLC management, fostering the development of more effective and comprehensive treatment modalities to ultimately enhance patient outcomes.
非小细胞肺癌(NSCLC)是一种全球性的健康威胁,表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)如吉非替尼、阿法替尼和奥希替尼在临床治疗中取得了显著的成功。然而,耐药性的出现限制了这些治疗的长期疗效,因此迫切需要探索新的 EGFR-TKIs。本综述深入总结和探讨了与 EGFR-TKIs 相关的耐药机制,特别关注吉非替尼、阿法替尼和奥希替尼等代表性药物。此外,该综述还介绍了一种涉及中草药(CHMs)和化疗药物联合治疗的策略,强调了 CHMs 在克服 NSCLC 耐药性方面的潜在作用。通过系统分析,我们阐明了 EGFR-TKIs 在 NSCLC 治疗中的主要耐药机制,强调了 CHMs 作为潜在的治疗药物,并为开发下一代 EGFR-TKIs 提供了新的视角。本综述旨在指导 CHMs 在 NSCLC 管理的联合治疗中的应用,促进更有效和全面的治疗方式的发展,最终改善患者的治疗效果。