自噬与非小细胞肺癌egfr-tki耐药的研究进展-中国细胞生物学学报.pdfVIP

中国细胞生物学学报 Chinese Journal of Cell Biology 2016, 38(9): 1144– 1151 DOI: 10.11844/cj cb.2016.09.0136 自噬与非小细胞肺癌EGFR-TKI耐药的研究进展 谢雨琼 李春春 曹 江* (浙江大学医学院附属第二医院, 临床研究中心, 杭州310009) 摘要 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。 关键词 非小细胞肺癌; 表皮生长因子受体; 酪氨酸激酶抑制剂; 获得性耐药; 自噬 Advances of Autophagy and EGFR-TKI Drug Resistance in the Treatment of Non-Small Cell Lung Cancer Xie Yuqiong, Li Chunchun, Cao Jiang* (Clinical Research Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China) Abstract 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. Keywords