肺癌黄金突变 ALK 的靶向治疗

ALK 的生理作用

间变性淋巴瘤激酶（ALK）也称为 ALK 酪氨酸激酶受体或 CD246（分化簇 246），在人类中，该酶由 ALK 基因编码[1]。

ALK 是一种受体酪氨酸激酶（RTK），由细胞外配体结合结构域、跨膜结构域和细胞内酪氨酸激酶结构域三个部分组成[2]。

与配体结合后，ALK 发生二聚化和自磷酸化。磷酸化的 ALK 激活多个下游信号转导通路，包括 MAPK-ERK、PI3K-AKT、PLCγ、CRKL-C3G 和 JAK-STAT[3,4]。天然 ALK 蛋白对神经系统的发育和功能至关重要[5]。

ALK 融合的致癌机制

ALK 的靶向治疗

ALK-TKI 靶向治疗的耐药问题

ALK 依赖性耐药

ALK 非依赖性耐药

ALK-TKI 耐药的应对策略

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