靶向ALK抑制剂的研究进展及前景

Research progress and prospect of targeted ALK inhibitors

随着分子生物医学研究的不断深入,以与肿瘤发生、发展相关的驱动基因为靶点,研发新的药物进行精准的个体化分子靶向治疗,已经成为肿瘤研究的新热点。间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)基因是一种跨膜受体酪氨酸激酶,可在多种恶性肿瘤中发生变异或与其他癌基因融合,是肿瘤的致癌驱动基因。近年来,ALK抑制剂在抗肿瘤、尤其是靶向肺癌方面的研究和应用一直保持了很高的研发热度。笔者针对已开发和在研的新型靶向ALK抑制剂的化学结构、研发进展、临床应用等方面进行了综述,并展望了ALK抑制剂的发展前景和需要解决的问题。

With the progress of molecular biomedical research, the research and development of new drugs for precise and individualized molecular targeted therapy has become a new hot point in the research of tumor, taking the driving genes related to tumorigenesis and development as the target. Anaplastic lymphoma kinase gene is a transmembrane receptor tyrosine kinase which can mutate or fuse with other oncogenes in many malignant tumors. In recent years, the research and application of ALK inhibitors in anti-tumor field, especially those targeting lung cancer has maintained a high degree of heat. In this paper, the chemical structure, research and development progress and clinical application of new targeted ALK inhibitors which have been developed and studied are reviewed. The prospect of ALK inhibitors and the problems that need to be solved are also prospected.