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癌基因观察站:靶向治疗指南

An Observatory for the Oncogene: A Guide for Targeted Therapies.

作者信息

Altintas Dogus M, Comoglio Paolo M

机构信息

IFOM ETS-The AIRC Institute of Molecular Oncology, 20139 Milano, Italy.

出版信息

Cancers (Basel). 2023 Sep 21;15(18):4672. doi: 10.3390/cancers15184672.

Abstract

The proto-oncogene encodes a pivotal tyrosine kinase receptor, binding the hepatocyte growth factor (HGF, also known as scatter factor, SF) and governing essential biological processes such as organogenesis, tissue repair, and angiogenesis. The pleiotropic physiological functions of MET explain its diverse role in cancer progression in a broad range of tumors; genetic/epigenetic alterations of drive tumor cell dissemination, metastasis, and acquired resistance to conventional and targeted therapies. Therefore, targeting MET emerged as a promising strategy, and many efforts were devoted to identifying the optimal way of hampering MET signaling. Despite encouraging results, however, the complexity of MET's functions in oncogenesis yields intriguing observations, fostering a humbler stance on our comprehension. This review explores recent discoveries concerning alterations in cancer, elucidating their biological repercussions, discussing therapeutic avenues, and outlining future directions. By contextualizing the research question and articulating the study's purpose, this work navigates MET biology's intricacies in cancer, offering a comprehensive perspective.

摘要

原癌基因编码一种关键的酪氨酸激酶受体,它结合肝细胞生长因子(HGF,也称为散射因子,SF)并调控器官发生、组织修复和血管生成等重要生物学过程。MET的多效生理功能解释了其在多种肿瘤的癌症进展中的不同作用;MET的遗传/表观遗传改变驱动肿瘤细胞播散、转移以及对传统疗法和靶向疗法产生获得性耐药。因此,靶向MET成为一种有前景的策略,人们致力于确定阻碍MET信号传导的最佳方法。然而,尽管取得了令人鼓舞的结果,但MET在肿瘤发生中的功能复杂性产生了有趣的观察结果,促使我们在理解上保持更谦逊的态度。本综述探讨了有关MET在癌症中改变的最新发现,阐明其生物学影响,讨论治疗途径并概述未来方向。通过将研究问题置于背景中并阐明研究目的,这项工作梳理了癌症中MET生物学的复杂性,提供了一个全面的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bed/10526818/312beedec21e/cancers-15-04672-g001.jpg

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