摘要
原肌球蛋白受体激酶(TRK) A, TRKA,是神经生长因子(NGF)的特异性结合受体,在人类癌症的发生和发展中起着至关重要的作用。TRKA过表达已被证明是一个强大的致癌驱动因素,并已在许多肿瘤中得到证实。TRKA受体激酶结构域以ngf依赖的方式过度激活,伴随着下游信号通路的激活,如RAS-MAPK、PI3K-AKT、JAK2-STAT3通路、PLC γ通路和Hippo通路,这些信号通路参与肿瘤细胞增殖、侵袭、上皮-间质转化(EMT)、神经周侵袭(PNI)、耐药和癌痛。此外,NTRK1与其他基因融合产生的嵌合癌基因也是肿瘤发生和癌症发展的直接原因。新开发的TRK抑制剂可以改善TRKA或NTRK1融合基因过表达的癌症患者的症状和肿瘤消退。随着耐药的出现,下一代TRK抑制剂在TRK激酶结构域突变的情况下仍能保持较强的临床疗效,这些抑制剂正在临床试验中。本文综述了TRKA的特点及研究进展,重点介绍了TRKA信号通路在不同肿瘤中的调控作用。此外,我们还总结了TRKA及TRK抑制剂的临床意义。本文综述可能为研究TRKA在不同肿瘤中的作用机制提供新的参考,也为深入了解TRKA作为生物标志物和治疗靶点在人类癌症中的作用提供新的视角。
关键词: TRKA, TRKA过表达,TRKA融合,TRKA抑制剂,靶向治疗,致瘤性。
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