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Genetically-engineered preclinical models predict pharmacodynamic response
Date:9/19/2012

New cancer drugs must be thoroughly tested in preclinical models, often in mice, before they can be offered to cancer patients for the first time in phase I clinical trials. Key components of this process include pharmacokinetic and pharmacodynamic studies, which evaluate how the drug acts on a living organism. These studies measure the pharmacologic response and the duration and magnitude of response observed relative to the concentration of the drug at an active site in the organism.

A new comparison of four different methodologies for pharmacokinetic and pharmacodynamic testing of the anti-melanoma agent carboplatin, demonstrates that genetically-engineered mouse models provide tumor delivery of drug most comparable to the response seen in melanoma patients.

"These studies are critically important in the case of small-molecule cancer drugs, which often have systemic side effects and can be toxic at high concentrations," said Ned Sharpless, MD, Wellcome Distinguished Professor of Cancer Research and study co-author.

The study, led by Bill Zamboni, PharmD and PhD, Associate Professor of Pharmacotherapy and Experimental Therapeutics at the UNC Eshelman School of Pharmacy and a member of UNC Lineberger Comprehensive Cancer Center, and Ned Sharpless, MD, who is also Associate Director for Translational Research at UNC Lineberger.

The collaborative study, which appears in The Oncologist, brought together a set of unique resources available at UNC to determine which preclinical models best predict delivery of carboplatin to melanoma tumors in patients. "We have a unique opportunity to evaluate an important factor in the treatment of solid tumors because of the outstanding collaborative nature and novel resources at UNC", said Zamboni.

"We have used a pharmacokinetics testing method called microdialysis, which uses a tiny probe to take samples that measure serial drug concentrations in a tumor over time," he ad
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Contact: Ellen de Graffenreid
edegraff@med.unc.edu
919-962-3405
University of North Carolina Health Care
Source:Eurekalert

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