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转运组学在肝细胞癌和肝胆管癌的药物基因组学中的作用。

Role of transportome in the pharmacogenomics of hepatocellular carcinoma and hepatobiliary cancer.

机构信息

Experimental Hepatology & Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca, 37007, Spain.

Center for the Study of Liver & Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, 28029, Spain.

出版信息

Pharmacogenomics. 2019 Aug;20(13):957-970. doi: 10.2217/pgs-2019-0033.

Abstract

An important factor determining the pharmacological response to antitumor drugs is their concentrations in cancer cells, which accounts for the net interaction with their intracellular molecular targets. Accordingly, mechanisms leading to reduced intracellular levels of active agents play a crucial role in cancer chemoresistance. These include impaired drug uptake through solute carrier (SLC) proteins and efficient drug export by ATP-dependent pumps belonging to the ATP-binding cassette (ABC) superfamily of proteins. Since the net movement of drugs in-and-out the cells depends on the overall expression of carrier proteins, defining the so-called transportome, special attention has been devoted to the study of transcriptome regarding these proteins. Nevertheless, genetic variants affecting and genes may markedly affect the bioavailability and, hence, the efficacy of anticancer drugs.

摘要

决定抗肿瘤药物药理反应的一个重要因素是它们在癌细胞中的浓度,这与它们与细胞内分子靶标的净相互作用有关。因此,导致细胞内活性药物水平降低的机制在癌症化疗耐药性中起着至关重要的作用。这些机制包括通过溶质载体 (SLC) 蛋白减少药物摄取和通过属于三磷酸腺苷 (ATP) 结合盒 (ABC) 蛋白超家族的 ATP 依赖性泵有效地将药物排出细胞外。由于药物进出细胞的净运动取决于载体蛋白的整体表达,即所谓的转运组,因此特别关注这些蛋白质的转录组研究。然而,影响 和 基因的遗传变异可能会显著影响抗癌药物的生物利用度,从而影响其疗效。

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