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

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

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


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.


Cancer; MDR; SLC proteins; chemoresistance; chemotherapy; pharmacology; transport

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