Pregnane X Receptor, Constitutive Androstane Receptor and Hepatocyte Nuclear Factors as Emerging Players in Cancer Precision Medicine

Abstract

Great research effort has been focused on elucidating the contribution of host genetic variability on pharmacological outcomes in cancer. Nuclear receptors have emerged as mediators between environmental stimuli and drug pharmacokinetics and pharmacodynamics. The pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factors have been reported to regulate transcription of genes that encode drug metabolizing enzymes and transporters. Altered nuclear receptor expression has been shown to affect the metabolism and pharmacological profile of traditional chemotherapeutics and targeted agents. Accordingly, polymorphic variants in these genes have been studied as pharmacogenetic markers of outcome variability. This review summarizes the state of knowledge about the roles played by pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factor expression and genetics as predictive markers of anticancer drug toxicity and efficacy, which can improve cancer precision medicine.

Keywords::

• cancer
• CAR
• chemotherapy
• HNFs
• inflammation
• metabolic enzymes
• pharmacogenetics
• polymorphisms
• PXR
• transporters

Financial & competing interests disclosure

This work was supported by the ‘Associazione Italiana per la Ricerca sul Cancro’ (AIRC; Special Program Molecular Clinical Oncology, 5x1000, [no. 12214]). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was provided by San Francisco Edit and funded by the ’Associazione Italiana per la Ricerca sul Cancro’ (AIRC; Special Program Molecular Clinical Oncology, 5x1000, [no. 12214]).

Additional information

Funding

This work was supported by the ‘Associazione Italiana per la Ricerca sul Cancro’ (AIRC; Special Program Molecular Clinical Oncology, 5x1000, [no. 12214]). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance was provided by San Francisco Edit and funded by the ’Associazione Italiana per la Ricerca sul Cancro’ (AIRC; Special Program Molecular Clinical Oncology, 5x1000, [no. 12214]).