Discovery of ALK Kinase Inhibitors as Targeted Therapeutics for Non-small Cell Lung Cancer

Abstract

肺癌是目前世界上第一大癌症,每年有近140万人死于肺癌,其中非小细胞肺癌(Non-smallCellLungCancer,NSCLC)占85%。研究表明激酶EML4-ALK是诱发产生一类NSCLC的关键基因,目前美国FDA已批准克唑替尼(Crizotinib)和色瑞替尼(Ceritinib)两个靶向EML4-ALK的抗非小细胞肺癌的激酶抑制剂药物,但随着获得性耐药突变的出现大大限制了药物治疗效果。为解决现有ALK激酶药物的选择性和耐药性问题,发展新颖的、高选择性的靶向ALK抗非小细胞肺癌药物具有十分重要的意义。 本论文主要进行了以下方面的研究: (1)基于激酶稳转的Ba/F3系细胞,建立了...Lung cancer is a leading cause of cancer mortality, accounting for approximately 1.4 million worldwide deaths each year. The non-small cell lung cancer (NSCLC) comprises about 85% of this disease. The chimeric protein of ALK and EML4, is prevalent in NSCLC, which constitutively activates downstream signals and leads to tumorigenesis. Currently, Crizotinib and Ceritinib, two small molecular inhibit...学位:理学博士院系专业:生命科学学院_微生物学学号:2162011015393

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