Understanding mechanisms involved in interindividual variability in anticancer drug disposition and bioavailability of hormonal drivers of cancer is required for more precise and efficient treatment of cancer and to prevent or delay recurrence after initial treatment.
Our overreaching goals are 1) to improve prediction of anticancer drug responses and prognosis for personalized therapeutic interventions; and 2) to provide a deeper understanding of the mechanisms involved in interindividual variability in drug metabolism and bioavailability of hormonal drivers of cancer, for more precise treatment of cancer patients.
Our research is focused in the area of steroids metabolism and their role in cancer. Another main aspect further examines the clinical impact of genetically variable metabolism by enzymes named UDP-GlucuronosylTransferase (UGTs). UGT enzymes display remarkable plasticity, affecting the bioactivity and bioavailability of a wide range of anticancer agents while controlling exposure to key drivers of cancer such as steroids.
To date, our work has clearly established a key role for steroids and the UGT metabolic pathway i) influencing patients’ response to drugs, ii) in the development and progression of various cancers with evidence of UGTs acting as disease accelerators for different cancers; iii) while developing mass spectrometry for quantitative and accurate measures of hormones and drugs.
Our current objectives are 1) to elucidate molecular mechanisms of variability in drugs and steroids metabolism using complementary models that integrate research on genomics and post-translational processes using cutting-edge technologies and 2) determine how this influence drug response and disease progression through studies of cancer patients. This is made possible owing to collaborative partnerships with clinicians recruiting patients and providing clinical data and specimens from large cohorts of cancer patients.
Outcomes and impact: This research offers high translational potential, as it will expand knowledge of anticancer drugs and steroids metabolism, and prognostic and predictive markers that will allow better therapeutic interventions tailored to cancer patients.
- Canada Research Chairs program (Canada Research Chair in Pharmacogenomics)
- Canadian Institutes of Health Research (CIHR)
- Canadian Innovation Foundation (FCI)
- National Sciences and Engineering Research Council of Canada (NSERC)