自噬与非小细胞肺癌EGFR-TKI耐药的研究进展

Advances of Autophagy and EGFR-TKI Drug Resistance in the Treatment of Non-Small Cell Lung Cancer

肺癌是目前世界上发病率和死亡率均居首位的恶性肿瘤,其中大多数是非小细胞肺癌(non-small cell lung cancer,NSCLC)。在对NSCLC的治疗中,酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)的应用已成为靶向表皮生长因子受体(epidermal growth factor receptor,EGFR)的重要治疗手段。但由于获得性耐药问题的出现,使得这类靶向药物的作用受到限制。近年来大量研究表明,除了基因突变等分子水平的因素外,细胞自噬(autophagy)在非小细胞肺癌EGFR-TKI靶向药物耐药中也发挥了重要的作用。该文重点就自噬与非小细胞肺癌EGFR-TKI靶向药物耐药的研究进展进行分析,旨在为解决自噬相关的EGFR-TKI耐药提供更多思路。

Lung cancer is currently the top malignancy with the highest morbidity and mortality worldwide, most of which belongs to non-small cell lung cancer（NSCLC）. Application of tyrosine kinase inhibitors（TKIs） has become an important therapeutic approach targeting epidermal growth factor receptor（EGFR） for treatment of NSCLC patients. However, the arising acquired-resistance significantly limits the efficacy of these targeting agents. Besides factors at molecular level such as genetic mutations, a number of investigations in recent years showed that autophagy played an important role in acquired-resistance to EGFR-TKIs of NSCLC. In this review, we focus on summarizing recent advances in autophagy and acquired-resistance to EGFR-TKIs of NSCLC, aiming to provide more ideas to overcome the autophagy-associated acquired-resistance to EGFR-TKI in NSCLC treatment.