Nuclear receptors and drug metabolism for the personalization of cancer therapy

Expert Opinion on Drug Metabolism & Toxicology
Erika CecchinGiuseppe Toffoli

Abstract

A remarkable inter-individual variability in the occurrence of severe side effects represents an ongoing challenge in cancer treatment. Significant research efforts have focused on elucidating the contribution of the host genetic variability, but only a few markers have been identified for use in clinical practice. Several studies demonstrated that PXR and CAR activation can affect the expression of genes involved in absorption, distribution, metabolism and excretion (ADME) of antineoplastic drugs. The study of the host genetic background of Pregnane X Receptor (PXR; NR1I2) and Constitutive Androstane Receptor (CAR; NR1I3 and NR1I4), represents a new and attractive strategy to discern variability in ADME of antineoplastic drugs. An update of the most important findings about investigational CAR and PXR pharmacogenetic markers of anti-cancer drugs toxicity is provided. A differential activation of PXR and CAR can affect the pharmacokinetics and pharmacodynamics of antineoplastic drugs. Pharmacogenetics studies published up to date provide encouraging even if exploratory results. Future large and prospective studies will clarify the clinical value of PXR and CAR genetic markers in treatment personalization.

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Citations

Sep 13, 2016·Nuclear Receptor Research·Satyanarayana R PondugulaSridhar Mani
Apr 19, 2020·Nature Reviews. Endocrinology·Karolien De BosscherLuc Brunsveld
May 24, 2017·Amino Acids·Liuqin HeYulong Yin

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