ABCG2: determining its relevance in clinical drug resistance View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-03

AUTHORS

Robert W. Robey, Orsolya Polgar, John Deeken, Kin Wah To, Susan E. Bates

ABSTRACT

Multidrug resistance is a major obstacle to successful cancer treatment. One mechanism by which cells can become resistant to chemotherapy is the expression of ABC transporters that use the energy of ATP hydrolysis to transport a wide variety of substrates across the cell membrane. There are three human ABC transporters primarily associated with the multidrug resistance phenomenon, namely Pgp, MRP1, and ABCG2. All three have broad and, to a certain extent, overlapping substrate specificities, transporting the major drugs currently used in cancer chemotherapy. ABCG2 is the most recently described of the three major multidrug-resistance pumps, and its substrates include mitoxantrone, topotecan, irinotecan, flavopiridol, and methotrexate. Despite several studies reporting ABCG2 expression in normal and malignant tissues, no trials have thus far addressed the role of ABCG2 in clinical drug resistance. This gives us an opportunity to critically review the disappointing results of past clinical trials targeting Pgp and to propose strategies for ABCG2. We need to know in which tumor types ABCG2 contributes to the resistance phenotype. We also need to develop standardized assays to detect ABCG2 expression in vivo and to carefully select the chemotherapeutic agents and clinical trial designs. This review focuses on our current knowledge about normal tissue distribution, tumor expression profiles, and substrates and inhibitors of ABCG2, together with lessons learned from clinical trials with Pgp inhibitors. Implications of SNPs in the ABCG2 gene affecting the pharmacokinetics of substrate drugs, including many non-chemotherapy agents and ABCG2 expression in the SP population of stem cells are also discussed. More... »

PAGES

39-57

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10555-007-9042-6

DOI

http://dx.doi.org/10.1007/s10555-007-9042-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1051227501

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17323127


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