Background: Breast Cancer Resistance Protein (BCRP, also known as ABCG2) is gaining momentum as
a key transporter that restricts the permeability of a large number of therapeutic agents through the Blood-brain Barrier
(BBB). BCRP is highly expressed in the apical membranes of epithelial cells of the small and large intestine,
renal proximal tubules and canalicular membrane of hepatocytes, determining the gastrointestinal absorption and
biodisposition of its substrates. It is also expressed in the luminal surface of endothelial cells of the BBB and Bloodspinal
Cord Barrier (BSCB), where it undoubtedly limits the entry of a wide range of therapeutics into the CNS,
potentially contributing to the therapeutic failure of CNS-acting drugs.
Methods: As the U.S. Food and Drug Administration and the European Medicines Agency recommend pre-clinical
evaluation and clinical assessment of BCRP-mediated drug-drug interactions, compounds that are currently recognized
as BCRP substrates, inhibitors or inducers will be addressed, focusing on their pharmacokinetic behaviour in
plasma and brain.
Results: Recent studies indicated a strong BCRP expression in the microvasculature of the BBB in brain tumors,
hypothesizing that this phenomenon critically influences the penetration of drugs in these tumors and potentially
contributes to the failure of antitumor therapy. BCRP expression in brain tissue from patients or animal models of
neurological and neurodegenerative diseases has also been investigated, and the role of BCRP and its implications
for novel therapeutic interventions was also herein demonstrated.
Conclusions: The clinical significance of BCRP in drugs disposition is currently undeniable.