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综述:美国食品药品监督管理局批准的针对乳腺癌女性的 MAPK 信号通路靶向药物。

Mini review: The FDA-approved prescription drugs that target the MAPK signaling pathway in women with breast cancer.

机构信息

Department of Obstetrics and Gynecology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

出版信息

Breast Dis. 2021;40(2):51-62. doi: 10.3233/BD-201063.

Abstract

Breast cancer (BC) is the most common cancer and the prevalent type of malignancy among women. Multiple risk factors, including genetic changes, biological age, dense breast tissue, and obesity are associated with BC. The mitogen-activated protein kinases (MAPK) signaling pathway has a pivotal role in regulating biological functions such as cell proliferation, differentiation, apoptosis, and survival. It has become evident that the MAPK pathway is associated with tumorigenesis and may promote breast cancer development. The MAPK/RAS/RAF cascade is closely associated with breast cancer. RAS signaling can enhance BC cell growth and progression. B-Raf is an important kinase and a potent RAF isoform involved in breast tumor initiation and differentiation. Depending on the reasons for cancer, there are different strategies for treatment of women with BC. Till now, several FDA-approved treatments have been investigated that inhibit the MAPK pathway and reduce metastatic progression in breast cancer. The most common breast cancer drugs that regulate or inhibit the MAPK pathway may include Farnesyltransferase inhibitors (FTIs), Sorafenib, Vemurafenib, PLX8394, Dabrafenib, Ulixertinib, Simvastatin, Alisertib, and Teriflunomide. In this review, we will discuss the roles of the MAPK/RAS/RAF/MEK/ERK pathway in BC and summarize the FDA-approved prescription drugs that target the MAPK signaling pathway in women with BC.

摘要

乳腺癌(BC)是最常见的癌症,也是女性中最常见的恶性肿瘤类型。多种风险因素,包括遗传改变、生物年龄、致密乳腺组织和肥胖,与 BC 相关。丝裂原活化蛋白激酶(MAPK)信号通路在调节细胞增殖、分化、凋亡和存活等生物学功能方面起着关键作用。已经明显表明,MAPK 途径与肿瘤发生有关,并可能促进乳腺癌的发展。MAPK/RAS/RAF 级联反应与乳腺癌密切相关。RAS 信号可以增强 BC 细胞的生长和进展。B-Raf 是一种重要的激酶,也是一种参与乳腺肿瘤起始和分化的有效 RAF 同工型。根据癌症的原因,有不同的策略来治疗患有 BC 的女性。到目前为止,已经研究了几种 FDA 批准的治疗方法,这些方法可以抑制 MAPK 途径并减少乳腺癌的转移进展。调节或抑制 MAPK 途径的最常见的乳腺癌药物可能包括法尼基转移酶抑制剂(FTIs)、索拉非尼、vemurafenib、PLX8394、dabrafenib、ulixertinib、辛伐他汀、alisertib 和特立氟胺。在这篇综述中,我们将讨论 MAPK/RAS/RAF/MEK/ERK 通路在 BC 中的作用,并总结 FDA 批准的针对 BC 女性 MAPK 信号通路的处方药。

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