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P-glycoprotein: So Many Ways to Turn It On

From Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom (Dr Callaghan and Miss Crowley); School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom (Mr Potter and Dr Kerr).

Expression of the ABC transporter P-glycoprotein (P-gp or ABCB1) is associated with resistance to chemotherapy in cancer. However, early investigations into the regulation of ABCB1 expression revealed that the process is not a classical induction as observed for certain metabolizing enzymes. The process involves the cellular stress response pathway initiated by either inflicted (eg, chemotherapy damage) or endogenous (eg, hypoxia) factors. However, ABCB1 is also expressed in a number of noncancerous tissues. In particular, the protein is found at tissues providing a barrier or secretory function. The localization of ABCB1 in normal tissues will impact significantly on drug pharmacokinetics, in particular the absorption and elimination processes. This review also describes the mechanism underlying ABCB1 expression in noncancerous tissue, a process that does not involve the stress response.

Key Words: P-glycoprotein • ABCB1 • drug resistance • chemotherapy • drug elimination • drug absorption

Address for correspondence: Dr Richard Callaghan, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK; e-mail: richard.callaghan{at}ndcls.ox.ac.uk.