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多形性胶质母细胞瘤(GBM):当前治疗方法及耐药机制概述

Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance.

作者信息

Wu Wei, Klockow Jessica L, Zhang Michael, Lafortune Famyrah, Chang Edwin, Jin Linchun, Wu Yang, Daldrup-Link Heike E

机构信息

Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 94305, USA.

Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.

出版信息

Pharmacol Res. 2021 Sep;171:105780. doi: 10.1016/j.phrs.2021.105780. Epub 2021 Jul 21.

Abstract

Glioblastoma multiforme (GBM) is a WHO grade IV glioma and the most common malignant, primary brain tumor with a 5-year survival of 7.2%. Its highly infiltrative nature, genetic heterogeneity, and protection by the blood brain barrier (BBB) have posed great treatment challenges. The standard treatment for GBMs is surgical resection followed by chemoradiotherapy. The robust DNA repair and self-renewing capabilities of glioblastoma cells and glioma initiating cells (GICs), respectively, promote resistance against all current treatment modalities. Thus, durable GBM management will require the invention of innovative treatment strategies. In this review, we will describe biological and molecular targets for GBM therapy, the current status of pharmacologic therapy, prominent mechanisms of resistance, and new treatment approaches. To date, medical imaging is primarily used to determine the location, size and macroscopic morphology of GBM before, during, and after therapy. In the future, molecular and cellular imaging approaches will more dynamically monitor the expression of molecular targets and/or immune responses in the tumor, thereby enabling more immediate adaptation of tumor-tailored, targeted therapies.

摘要

多形性胶质母细胞瘤(GBM)是世界卫生组织IV级胶质瘤,也是最常见的恶性原发性脑肿瘤,其5年生存率为7.2%。其高度浸润性、基因异质性以及血脑屏障(BBB)的保护作用给治疗带来了巨大挑战。GBM的标准治疗方法是手术切除,然后进行放化疗。胶质母细胞瘤细胞和胶质瘤起始细胞(GICs)分别具有强大的DNA修复和自我更新能力,这促进了它们对所有现有治疗方式的抗性。因此,持久的GBM治疗需要创新治疗策略。在这篇综述中,我们将描述GBM治疗的生物学和分子靶点、药物治疗现状、主要抗性机制以及新的治疗方法。迄今为止,医学成像主要用于在治疗前、治疗期间和治疗后确定GBM的位置、大小和宏观形态。未来,分子和细胞成像方法将更动态地监测肿瘤中分子靶点的表达和/或免疫反应,从而能够更迅速地调整针对肿瘤的靶向治疗。

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