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揭示“癌症基因组图谱”中 SLC 转运体在抗癌药物摄取中的作用信息。

Unraveling 'The Cancer Genome Atlas' information on the role of SLC transporters in anticancer drug uptake.

机构信息

a Experimental Hepatology and Drug Targeting (HEVEFARM) , University of Salamanca, IBSAL , Salamanca , Spain.

b Department of Physiology and Pharmacology , Sapienza University of Rome , Rome , Italy.

出版信息

Expert Rev Clin Pharmacol. 2019 Apr;12(4):329-341. doi: 10.1080/17512433.2019.1581605. Epub 2019 Feb 26.

Abstract

Anticancer chemotherapy often faces the problem of intrinsic or acquired drug refractoriness due in part to efficient mechanisms of defense present or developed, respectively, in cancer cells. Owing to their polarity and/or high molecular weight, many cytostatic agents cannot freely cross the plasma membrane by simple diffusion and hence depend on SLC proteins to enter cancer cells. The downregulation of these transporters and the appearance of either inactivating mutations or aberrant splicing, hamper the possibility of anticancer drugs to interact with their intracellular targets. Areas covered: In addition to specific literature, we have revised Gene database of the NCBI PubMed resources and information publicly available at NIH 'The Cancer Genome Atlas' (TCGA) (update November 2018) to evaluate the relationship between the profile of expression of SLC transporters playing a major role in the transportome and accounting for drug uptake, in healthy and tumor tissue, and their ability to recognize as substrate several antitumor drugs frequently used in the treatment of different types of cancer, which could affect the overall response to chemotherapy based on regimens including these drugs. Expert commentary: Changes in the transportome may affect the overall response to chemotherapy based on drugs taken up by SLC transporters.

摘要

抗癌化疗常常面临内在或获得性耐药的问题,部分原因是癌细胞中存在或分别发展的有效的防御机制。由于其极性和/或高分子量,许多细胞抑制剂不能通过简单扩散自由穿过质膜,因此依赖 SLC 蛋白进入癌细胞。这些转运蛋白的下调以及失活突变或异常剪接的出现,阻碍了抗癌药物与细胞内靶标相互作用的可能性。涵盖领域:除了特定的文献,我们还修订了 NCBI PubMed 资源的基因数据库和 NIH 公共信息'癌症基因组图谱'(TCGA)(2018 年 11 月更新),以评估在转运体中起主要作用并负责药物摄取的 SLC 转运蛋白的表达谱与健康和肿瘤组织之间的关系,以及它们识别几种常用于治疗不同类型癌症的抗肿瘤药物作为底物的能力,这可能会影响基于包括这些药物在内的方案的化疗总体反应。专家评论:转运体的变化可能会影响基于 SLC 转运体摄取的药物的化疗总体反应。

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