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非小细胞肺癌靶向治疗药物的研究进展

Advances in research on drugs targeting non-small cell lung cancer

【作者】 赵雷磊张媛周金培张惠斌

【Author】 ZHAO Leilei;ZHANG Yuan;ZHOU Jinpei;ZHANG Huibin;Center of Drug Discovery,China Pharmaceutical University;

【机构】 中国药科大学新药研究中心

【摘要】 研究发现非小细胞肺癌形成与多种致癌突变密切相关,如表皮生长因子受体(EGFR)突变、间变性淋巴瘤激酶(ALK)重排以及肝细胞生长因子受体(c-MET)扩增等。本文从腺癌和鳞状细胞癌两个亚型的靶向治疗药物入手,分别介绍了非小细胞肺癌潜在的靶点及小分子抑制剂,包括EGFR抑制剂、ALK抑制剂、KRAS抑制剂、c-MET抑制剂、FGFR1抑制剂、PI3K抑制剂、BRAF抑制剂、ERBB2抑制剂以及DDR2抑制剂,为非小细胞肺癌患者临床用药和非小细胞肺癌靶向治疗药物开发提供参考。

【Abstract】 With the continuous development of molecular biology,people have gained a deeper understanding of non-small cell lung cancer( NSCLC). Researchers have found that multiple oncogenic driver mutations are closely associated with the development,progression and prognosis of NSCLC,such as EGFR mutations,ALK rearrangement,KRAS mutations,c-MET amplification,FGFR1 amplification,PIK3CA mutations,BRAF mutations,ERBB2 amplification,and DDR2 mutation. Adenocarcinoma( ADC) and squamous cell carcinoma( SCC) are two most common subtypes of NSCLC. In this review,we choose targeted therapy drugs of ADC and SCC as an entry point to introduce several potential targets and small molecule inhibitors for the treatment of NSCLC,including EGFR inhibitors,ALK inhibitors,KRAS inhibitors,c-MET inhibitors,FGFR1 inhibitors,PI3K inhibitors,BRAF inhibitors,ERBB2 inhibitors and DDR2 inhibitors. We hope this review will be a helpful guide to clinicians and researchers alike by assisting in therapy decision making and acting as a platform for further study.

【关键词】 非小细胞肺癌; 腺癌; 鳞状细胞癌; 致癌突变; 小分子抑制剂; 靶向药物;

【Key words】 non-small cell lung cancer; adenocarcinoma; squamous cell carcinoma; oncogenic driver mutation; small molecular inhibitor; targeting drugs;

【分类号】R734.2;R456.9;R730.267.9;

【基金】 国家"重大新药创制"科技重大专项资助项目(No.2013ZX09301303-002)~~

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