Abstract: AbstractChemotherapy is one of the three most common treatment modalities for cancer. However, chemotherapy as current firstline therapy induces significant side effects and limited efficacy, leading to multidrug resistance and fast recurrence challenging the patient survival rate. Drug metabolizing enzymes (DMEs) and efflux transporters promote the metabolism, clearance, and detoxification of chemotherapeutic agents. Nuclear receptors, especially pregnane X receptor (PXR, NR112) and constitutive androstane activated receptor (CAR, NR113), regulate the expressions of target genes that could encode phase I DMEs, phase II DMEs, and efflux transporters in the development of multidrug resistance (MDR) during chemotherapy. Recent studies have revealed that PXR and CAR play pivotal roles in MDR of various human carcinomas. And their expression levels or activation statuses could predict the risk of drug resistance in patients subjected to chemotherapy. Accordingly, PXR/CAR antagonists, combining with existing chemotherapeutics that activate PXR/CAR, are promising options that could overcome MDR in cancer.

Key words: Cancer, Multidrug resistance, PXR , CAR