What “The Cancer Genome Atlas” database tells us about the role of ATP-binding cassette (ABC) proteins in chemoresistance to anticancer drugs

ABSTRACT

Introduction: Chemotherapy remains the only option for advanced cancer patients when other alternatives are not feasible. Nevertheless, the success rate of this type of therapy is often low due to intrinsic or acquired mechanisms of chemoresistance. Among them, drug extrusion from cancer cells through ATP-binding cassette (ABC) proteins plays an important role. ABC pumps are primary active transporters involved in the barrier and secretory functions of many healthy cells.

Areas covered: In this review, we have used The Cancer Genome Atlas (TCGA) database to explore the relationship between the expression of the major ABC proteins involved in cancer chemoresistance in the most common types of cancer, and the drugs used in the treatment of these tumors that are substrates of these pumps.

Expert opinion: From unicellular organisms to humans, several ABC proteins play a major role in detoxification processes. Cancer cells exploit this ability to protect themselves from cytostatic drugs. Among the ABC pumps, MDR1, MRPs and BCRP are able to export many antitumor drugs and are expressed in several types of cancer, and further up-regulated during treatment. This event results in the enhanced ability of tumor cells to reduce intracellular drug concentrations and hence the pharmacological effect of chemotherapy.

KEYWORDS:

• ABC proteins
• cancer
• chemoresistance
• chemotherapy
• MDR
• pharmacology
• transport

Article highlights

• High expression of ABC proteins in tumors contributes to the clinical failure of pharmacological regimens.

• Databases such as TCGA are useful for the identification of genes encoding ABC proteins highly expressed in cancer.

• Comparison of expression data with the extrusion capacity of the transporters can explain selective chemoresistance.

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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 paper was funded by the CIBERehd [EHD15PI05/2016] and Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain [PI16/00598, co-funded by European Regional Development Fund/European Social Fund, ‘Investing in your future’]; Spanish Ministry of Economy, Industry and Competitiveness [SAF2016-75197-R]; Junta de Castilla y Leon [SA063P17]; Fundación Mutua Madrileña, Spain (Call 2015); Fundación Samuel Solórzano Barruso, Spain [FS/7-2016, FS/8-2017 and FS/13-2017]; 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 (PFIS) funded by Instituto de Salud Carlos III, Spain and the European Social Fund (ESF)  [FI17/00149].