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MET癌基因:靶向治疗策略的最新进展

The MET Oncogene: An Update on Targeting Strategies.

作者信息

Gallo Simona, Folco Consolata Beatrice, Crepaldi Tiziana

机构信息

Department of Oncology, University of Turin, Regione Gonzole 10, 10143 Orbassano, Italy.

Candiolo Cancer Institute, FPO-IRCCS, SP142, Km 3.95, 10060 Candiolo, Italy.

出版信息

Pharmaceuticals (Basel). 2024 Nov 2;17(11):1473. doi: 10.3390/ph17111473.

Abstract

The MET receptor, commonly known as HGF (hepatocyte growth factor) receptor, is a focus of extensive scientific research. MET has been linked to embryonic development, tissue regeneration following injury, tumorigenesis, and cancer metastasis. These functions underscore its involvement in numerous cellular processes, including stemness, proliferation, motility, cell dissociation, and survival. However, the enigmatic nature of MET becomes apparent in the context of cancer. When MET remains persistently activated, since its gene undergoes genetic alterations, it initiates a complex signaling cascade setting in motion an aggressive and metastatic program that is characteristic of malignant cells and is known as "invasive growth". The expanding knowledge of MET signaling has opened up numerous opportunities for therapeutic interventions, particularly in the realm of oncology. Targeting MET presents a promising strategy for developing novel anti-cancer treatments. In this review, we provide an updated overview of drugs designed to modulate MET signaling, highlighting MET kinase inhibitors, degraders, anti-MET/HGF monoclonal antibodies, and MET-targeted antibody-drug conjugates. Through this review, we aim to contribute to the ongoing advancement of therapeutic strategies targeting MET signaling.

摘要

MET受体,通常被称为肝细胞生长因子(HGF)受体,是广泛科学研究的焦点。MET与胚胎发育、损伤后的组织再生、肿瘤发生和癌症转移有关。这些功能强调了它参与众多细胞过程,包括干性、增殖、运动性、细胞解离和存活。然而,MET的神秘性质在癌症背景下变得明显。当MET由于其基因发生遗传改变而持续激活时,它会启动一个复杂的信号级联反应,启动一个具有侵袭性和转移性的程序,这是恶性细胞的特征,被称为“侵袭性生长”。对MET信号通路的不断了解为治疗干预开辟了许多机会,特别是在肿瘤学领域。靶向MET为开发新型抗癌治疗提供了一个有前景的策略。在这篇综述中,我们提供了旨在调节MET信号通路的药物的最新概述,重点介绍了MET激酶抑制剂、降解剂、抗MET/HGF单克隆抗体和MET靶向抗体药物偶联物。通过这篇综述,我们旨在为针对MET信号通路的治疗策略的持续发展做出贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f12/11597589/4e5b444e9469/pharmaceuticals-17-01473-g001.jpg

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