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

ABSTRACT

Introduction: 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.

KEYWORDS:

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

Article highlights

• Many anticancer drugs depend on SLC transporter to reach intracellular targets

• SLC genes down-regulation and expression of inactive variants often occur in cancer

• Altered transportome may affect the overall response to anticancer chemotherapy

This box summarizes key points contained in the article.

Acknowledgments

The authors thank Emma Keck for revision of the English language.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by the CIBERehd [EHD15PI05/2016] and Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI16/00598, co-funded by the European Regional Development Fund/European Social Fund, ‘Investing in your future’); the Spanish Ministry of Economy, Industry and Competitiveness [SAF2016-75197-R]; the Regional Government of Castilla y León [SA063P17]; The Samuel Solórzano Barruso Memorial Foundation, Spain [FS/7-2016, FS/8-2017 and FS/13-2017]; and the AECC Scientific Foundation [2017/2020], Spain. R Al Abdulla was supported by a pre-doctoral contract funded by the ‘Junta de Castilla y León’ and the ‘Fondo Social Europeo’, Spain [EDU/828/2014]. L Perez-Silva was supported by a pre-doctoral contract funded by Instituto de Salud Carlos III y el Fondo Social Europeo (PFIS), Spain [FI17/00149].