针对胶质母细胞瘤中RTK/Ras/PI3K、p53或Rb信号通路的小分子疗法的药物反应遗传生物标志物。
Genetic biomarkers of drug response for small-molecule therapeutics targeting the RTK/Ras/PI3K, p53 or Rb pathway in glioblastoma.
作者信息
Venkatesan Subramanian, Lamfers Martine L M, Dirven Clemens M F, Leenstra Sieger
机构信息
Department of Neurosurgery, Brain Tumor Center of the Erasmus Medical Center, Rotterdam, The Netherlands.
UCL Cancer Institute, Paul O'Gorman Building, London, UK.
出版信息
CNS Oncol. 2016;5(2):77-90. doi: 10.2217/cns-2015-0005. Epub 2016 Mar 17.
Abstract
Glioblastoma is the most deadly and frequently occurring primary malignant tumor of the central nervous system. Genomic studies have shown that mutated oncogenes and tumor suppressor genes in glioblastoma mainly occur in three pathways: the RTK/Ras/PI3K signaling, the p53 and the Rb pathways. In this review, we summarize the modulatory effects of genetic aberrations in these three pathways to drugs targeting these specific pathways. We also provide an overview of the preclinical efforts made to identify genetic biomarkers of response and resistance. Knowledge of biomarkers will finally promote patient stratification in clinical trials, a prerequisite for trial design in the era of precision medicine.
摘要
胶质母细胞瘤是中枢神经系统最致命且最常见的原发性恶性肿瘤。基因组研究表明，胶质母细胞瘤中突变的癌基因和肿瘤抑制基因主要发生在三条途径中：RTK/Ras/PI3K信号传导途径、p53途径和Rb途径。在本综述中，我们总结了这三条途径中的基因异常对靶向这些特定途径的药物的调节作用。我们还概述了为确定反应和耐药的遗传生物标志物所做的临床前研究工作。生物标志物的知识最终将促进临床试验中的患者分层，这是精准医学时代试验设计的先决条件。
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