Preventing Adverse Patient Responses to Cancer Chemotherapeutics
Technical Report,01 Jun 2018,31 May 2019
Albert Einstein College of Medicine New York United States
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The purpose of this project is to prevent adverse patient responses to the cancer drug irinotecan by analyzing the gut microbiomes of patients. The scope of this project is to study irinotecan metabolism and the microbiome over time using fecal samples from healthy individuals and metastatic colorectal cancer patients. We have several major findings from the past year of work. We observe that betaglucuronidase BGs enzyme distribution differs between healthy and a metastatic colorectal cancer patient gut, and we highlight colorectal cancer-specific BGs that may be good biomarkers or targets for predicting or altering metabolism of the colorectal cancer drug irinotecan. We have enrolled colorectal cancer patients and collected samples. We have demonstrated that irinotecan metabolism in fecal samples does not overlap with that of another glucuronidated drug, indomethacin. We have discovered foods and supplements that may interfere with irinotecan metabolism in the gut and have published this work in the journal eLife Guthrie, et al, 2019. We have written a review to describe the difficulties and potential benefits of translating basic research on microbiome drug metabolism into the clinic and have published this work in the journal eBioMedicine Guthrie and Kelly, 2019. We have written a review that gives pharmacologists a framework for understanding how microbial enzymes can metabolize drugs and have published this work in the journal Trends in Pharmacological Sciences Hitchings and Kelly, 2019.
- Medicine and Medical Research