Apical ABC transporters and cancer chemotherapeutic drug disposition

Adv Cancer Res. 2015;125:1-41. doi: 10.1016/bs.acr.2014.10.001. Epub 2015 Jan 8.


ATP-binding cassette (ABC) transporters are transmembrane efflux transporters that mediate cellular extrusion of a broad range of substrates ranging from amino acids, lipids, and ions to xenobiotics including many anticancer drugs. ABCB1 (P-GP) and ABCG2 (BCRP) are the most extensively studied apical ABC drug efflux transporters. They are highly expressed in apical membranes of many pharmacokinetically relevant tissues such as epithelial cells of the small intestine and endothelial cells of the blood capillaries in brain and testis, and in the placental maternal-fetal barrier. In these tissues, they have a protective function as they efflux their substrates back to the intestinal lumen or blood and thus restrict the intestinal uptake and tissue disposition of many compounds. This presents a major challenge for the use of many (anticancer) drugs, as most currently used anticancer drugs are substrates of these transporters. Herein, we review the latest findings on the role of apical ABC transporters in the disposition of anticancer drugs. We discuss that many new, rationally designed anticancer drugs are substrates of these transporters and that their oral availability and/or brain disposition are affected by this interaction. We also summarize studies that investigate the improvement of oral availability and brain disposition of many cytotoxic (e.g., taxanes) and rationally designed (e.g., tyrosine kinase inhibitor) anticancer drugs, using chemical inhibitors of these transporters. These findings provide a better understanding of the importance of apical ABC transporters in chemotherapy and may therefore advance translation of promising preclinical insights and approaches to clinical studies.

Keywords: ABC transporters; Brain disposition; Chemotherapeutics; Drug disposition; Oral availability.

Publication types

  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / therapeutic use
  • Biological Availability
  • Biological Transport / physiology
  • Blood-Brain Barrier / physiology
  • Bridged-Ring Compounds / metabolism
  • Bridged-Ring Compounds / pharmacokinetics
  • Bridged-Ring Compounds / therapeutic use
  • Drug Resistance, Neoplasm / physiology*
  • Humans
  • Intestinal Absorption / physiology
  • Mice
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Taxoids / metabolism
  • Taxoids / pharmacokinetics
  • Taxoids / therapeutic use


  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Bridged-Ring Compounds
  • Taxoids
  • taxane