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乳腺癌生物学中的甲羟戊酸途径。

The mevalonate pathway in breast cancer biology.

机构信息

Mildred Scheel Early Career Center, Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Mildred Scheel Early Career Center, Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III, Technische Universität Dresden, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany.

出版信息

Cancer Lett. 2022 Aug 28;542:215761. doi: 10.1016/j.canlet.2022.215761. Epub 2022 May 28.

Abstract

Breast cancer affects one in eight women during their lifetime. Although diagnostic and therapeutic options have improved, recurrence, metastasis, and therapeutic resistance remain clinical challenges, which affect life quality and prognosis. The mevalonate pathway is an essential part of cellular homeostasis by providing a number of essential isoprenoid products including cholesterol. However, the disturbance of this pathway paralleled by increased bioavailability of its products and their direct involvement in several steps of tumorigenesis has highlighted the mevalonate pathway as a promising hub in cancer treatment. In this review, we will specifically discuss how the mevalonate pathway affects breast cancer biology in terms of supporting and modulating soluble and cellular factors and distinct steps of tumorigenesis. We will further summarize antitumor effects of the mevalonate pathway-inhibiting drugs, statins and amino-bisphosphonates, in breast cancer and discuss how they are used for future precision therapy.

摘要

乳腺癌在女性一生中影响八分之一的人。尽管诊断和治疗选择有所改善,但复发、转移和治疗耐药仍然是临床挑战,影响生活质量和预后。甲羟戊酸途径是细胞内稳态的重要组成部分,通过提供许多必需的异戊二烯产物,包括胆固醇。然而,该途径的紊乱伴随着其产物生物利用度的增加及其直接参与肿瘤发生的几个步骤,突出了甲羟戊酸途径作为癌症治疗有希望的枢纽。在这篇综述中,我们将专门讨论甲羟戊酸途径如何通过支持和调节可溶性和细胞因子以及肿瘤发生的不同步骤来影响乳腺癌生物学。我们将进一步总结甲羟戊酸途径抑制药物、他汀类药物和氨基双膦酸盐在乳腺癌中的抗肿瘤作用,并讨论它们如何用于未来的精准治疗。

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