Role of pregnane X receptor in chemotherapeutic treatment

Abstract

Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily that differently expresses not only in human normal tissues but also in numerous types of human cancers. PXR can be activated by many endogenous substances and exogenous chemicals, and thus affects chemotherapeutic effects and intervenes drug-drug interactions by regulating its target genes involving drug metabolism and transportation, cell proliferation and apoptosis, and modulating endobiotic homeostasis. Tissue and context-specific regulation of PXR contributes to diverse effects in the treatment for numerous cancers. Genetic variants of PXR lead to intra- and inter-individual differences in the expression and inducibility of PXR, resulting in different responses to chemotherapy in PXR-positive cancers. The purpose of this review is to summarize and discuss the role of PXR in the metabolism and clearance of anticancer drugs. It is also expected that this review will provide insights into PXR-mediated enhancement for chemotherapeutic treatment, prediction of drug-drug interactions and personalized medicine.

Fig. 1

PXR regulation of expression of genes for DMEs, transporters and cell process [11]. Upon binding to ligands, PXR dissociates from heat shock protein (HSP), trans-locates into nucleus, forms PXR/RXR heterodimer and stimulates the transcription of target genes, which lead to altered cell functions such as resistance to chemotherapy