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间变性淋巴瘤激酶:在癌症中的作用及治疗前景

Anaplastic lymphoma kinase: Role in cancer and therapy perspective.

作者信息

Zhao Zhihong, Verma Vivek, Zhang Mutian

机构信息

a Munroe-Meyer Institute; University of Nebraska Medical Center ; Omaha , NE , USA.

b Department of Radiation Oncology ; University of Nebraska Medical Center ; Omaha , NE , USA.

出版信息

Cancer Biol Ther. 2015;16(12):1691-701. doi: 10.1080/15384047.2015.1095407.

Abstract

Anaplastic lymphoma kinase (ALK) is correlated with oncogenesis in different types of cancers, such as anaplastic large cell lymphoma, lung cancer, neuroblastoma, and even breast cancer, by abnormal fusion of ALK or non-fusion ALK activation. ALK is a receptor tyrosine kinase, with a single transmembrane domain, that plays an important role in development. Upon ligand binding to the extracellular domain, the receptor undergoes dimerization and subsequent autophosphorylation of the intracellular kinase domain. In recent years, ALK inhibitors have been developed for cancer treatment. These inhibitors target ALK activity and show effectiveness in ALK-positive non-small cell lung cancer. However, acquired treatment resistance makes the future of this therapy unclear; new strategies are underway to overcome the limitations of current ALK inhibitors.

摘要

间变性淋巴瘤激酶(ALK)通过ALK的异常融合或非融合ALK激活,与不同类型癌症的肿瘤发生相关,如间变性大细胞淋巴瘤、肺癌、神经母细胞瘤,甚至乳腺癌。ALK是一种受体酪氨酸激酶,具有单个跨膜结构域,在发育过程中起重要作用。当配体与细胞外结构域结合时,受体会发生二聚化,随后细胞内激酶结构域发生自磷酸化。近年来,已开发出ALK抑制剂用于癌症治疗。这些抑制剂靶向ALK活性,并在ALK阳性非小细胞肺癌中显示出疗效。然而,获得性治疗耐药性使得这种治疗的前景不明朗;正在探索新的策略来克服当前ALK抑制剂的局限性。

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