Influence of serum inflammatory cytokines on cytochrome P450 drug metabolising activity during breast cancer chemotherapy: a patient feasibility study
Abstract
Individual response to chemotherapy in patients with breast cancer is variable. Obesity and exercise are associated with better and worse outcomes, respectively, and it is known that both impact the systemic cytokine milieu. Cytochrome P450 (CYP) enzymes are responsible for the metabolism of many chemotherapy agents, and CYP enzyme activity has been shown to be modified by inflammatory cytokines in vitro and in vivo. Cytokine-associated changes in CYP metabolism may alter chemotherapy exposure, potentially affecting treatment response and patient survival. Therefore, better understanding of these biological relationships is required. This exploratory single arm open label trial investigated changes in in vivo CYP activity in twelve women treated for stage II or III breast cancer, and demonstrated for the first time the feasibility and safety of utilising the Inje phenotyping cocktail to measure CYP activity in cancer patients receiving chemotherapy. Relative CYP activity varied between participants, particularly for CYP2C9 and CYP2D6, and changes in serum concentrations of the inflammatory cytokine monocyte chemoattractant protein 1 inversely correlated to CYP3A4 activity during chemotherapy. Future use of phenotyping cocktails in a clinical oncology setting may help guide drug dosing and improve chemotherapy outcomes.Clinical Trial Registration: Trial was retrospectively registered to the Australia New Zealand Clinical Trial Registry (ANZCTR). ACTRN12620000832976, 21 Aug…
How strong is the evidence?
Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
Read the paper
Related studies
- A Coupled SYSTEM of Intracellular Ca 2+ Clocks and Surface Membrane Voltage Clocks Controls the Timekeeping Mechanism of the Heart’s Pacemaker
- A Comprehensive Review on the Therapeutic Potential of Curcuma longa Linn. in Relation to its Major Active Constituent Curcumin
- Cancer epigenetics: Moving forward
- Current developments in LC-MS for pharmaceutical analysis
- Myricetin: A comprehensive review on its biological potentials
- A Computational Systems Biology Software Platform for Multiscale Modeling and Simulation: Integrating Whole-Body Physiology, Disease Biology, and Molecular Reaction Networks
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.