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乐伐替尼在肝癌中的作用机制和耐药机制。

The action and resistance mechanisms of Lenvatinib in liver cancer.

机构信息

Departments of Surgery, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA.

Departments of Cancer Biology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA.

出版信息

Mol Carcinog. 2023 Dec;62(12):1918-1934. doi: 10.1002/mc.23625. Epub 2023 Sep 6.

Abstract

Lenvatinib is a tyrosine kinase inhibitor that prevents the formation of new blood vessels namely by inhibiting tyrosine kinase enzymes as the name suggests. Specifically, Lenvatinib acts on vascular endothelial growth factor receptors 1-3 (VEGFR1-3), fibroblast growth factor receptors 1-4 (FGFR1-4), platelet-derived growth factor receptor-alpha (PDGFRα), tyrosine-kinase receptor (KIT), and rearranged during transfection receptor (RET). Inhibition of these receptors works to inhibit tumor proliferation. It is through these inhibition mechanisms that Lenvatinib was tested to be noninferior to Sorafenib. However, resistance to Lenvatinib is common, making the positive effects of Lenvatinib on a patient's survival null after resistance is acquired. Therefore, it is crucial to understand mechanisms related to Lenvatinib resistance. This review aims to piece together various mechanisms involved in Lenvatinib resistance and summarizes the research done so far investigating it.

摘要

乐伐替尼是一种酪氨酸激酶抑制剂,通过抑制酪氨酸激酶酶(顾名思义)来阻止新血管的形成。具体来说,乐伐替尼作用于血管内皮生长因子受体 1-3(VEGFR1-3)、成纤维细胞生长因子受体 1-4(FGFR1-4)、血小板衍生生长因子受体-α(PDGFRα)、酪氨酸激酶受体(KIT)和转染重排受体(RET)。这些受体的抑制作用可抑制肿瘤增殖。正是通过这些抑制机制,乐伐替尼被测试为不劣于索拉非尼。然而,乐伐替尼耐药很常见,耐药后乐伐替尼对患者生存的积极影响就会消失。因此,了解与乐伐替尼耐药相关的机制至关重要。本综述旨在梳理乐伐替尼耐药涉及的各种机制,并总结目前对其的研究。

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