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Alison Harrill, PhD, Assistant Professor in the COPH Department of Environmental and Occupational Health, has been awarded a $71,293, one-year grant for research that may lead to better health outcomes for patients undergoing chemotherapy with a particular drug, cisplatin.
Cisplatin and other drugs of its class are used to treat many types of cancer, but these drugs are associated with severe adverse events that can result in damage to the kidneys, hearing or nerves. The ability to measure and accurately monitor for cisplatin-induced kidney injury in patients is hindered by a lack of sensitivity in the biomarkers currently used to detect changes in kidney function.
Because differences in genetic sequences can affect susceptibility to drug-induced adverse events, Dr. Harrill plans on using a mouse population, the Diversity Outbred, in the study. The mouse stock was specially bred to reflect human population diversity. Using the Diversity Outbred will enable a translational epidemiological approach that will allow for estimation of variability of cisplatin-induced adverse events in human populations.
All mice in the study will be treated with cisplatin, and miRNA molecules will be measured in their urine to determine if they are more effective biomarkers for renal-injury susceptibility than the protein biomarkers currently in use in the clinic. These miRNA leak out of kidney cells into the urine when the cells become damaged due to cisplatin exposure.
“These studies have the potential to inform study designs for future studies that may impact personalized prescribing of cisplatin antitumor therapy,” Dr. Harrill said. “Through these studies, we aim to discover predictive biomarkers in mice that may in the future enable physicians to more accurately monitor for kidney injury caused by cisplatin chemotherapy in sensitive patients.”