Japanese  
  Home  |  Top News  |  Most Popular  |  Video  |  Multimedia  |  News Feeds  |  Feedback
  Medicine  |  Nature & Earth  |  Biology  |  Technology & Engineering  |  Space & Planetary  |  Psychology  |  Physics & Chemistry  |  Economics  |  Archaeology
Top > Medicine, Health Care > Genetically-engineered Preclinical Models Predict Pharmacodynamic… >
Genetically-engineered Preclinical Models Predict Pharmacodynamic Response

Published: September 19, 2012.
By University of North Carolina Health Care
http://www.med.unc.edu

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 added. "We plan to use this method to advance pharmacology studies of anticancer agents in tumors and tissues of patients and to evaluate the tumor delivery of nanoparticles and other classes of delivery agents."

The team used the resources of the preclinical phase I unit at UNC Lineberger to compare how pharmacokenetic levels vary in several preclinical tumor models including a genetically-engineered model, a model where tumor cells are transplanted to the appropriate part of the body (called an orthotopic syngeneic transplant or OST), and a xenograft model, where human tumor tissue is transplanted.

"Because carboplatin is widely used, we have good data on how the drug works pharmacokenetically in humans. For the first time, we were able to compare these various laboratory techniques used in countless labs and the pharmaceutical industry to evaluate how carboplatin was delivered to the tumor and compare it to actual human data. None of these laboratory models are perfect, but the genetically-engineered model is the best in terms of predicting the amount of drug that is delivered to the tumor in human patients," Zamboni added.

"We know that laboratory models are imperfectly predictive of human response and if the tumor models don't predict delivery, they are most likely not an optimal research tools," he noted.

Sharpless added, "We are continually looking for ways to build better laboratory models so that new therapies move from the lab to the patient as quickly and safely as possible. This study provides valuable validation that genetically-engineered models can help us accomplish this objective."


Show Reference »


Translate this page: Chinese French German Italian Japanese Korean Portuguese Russian Spanish


 
This is form to send feedback to the editors. Tell us what you think about this article. All comments are not published. If you are looking for a response to a question please use our another feedback page.
Related »

Tumor 
11/16/11 
New Stanford Model Establishes Guidelines for Earlier Cancer Detection
By Stanford University Medical Center
Tumors can grow for 10 years or longer before currently available blood tests will detect them, a new mathematical model developed by Stanford University School of Medicine scientists indicates. …
Tests 
8/1/13 
A Roadblock to Personalized Cancer Care?
By University of Michigan Health System
ANN ARBOR, Mich. β€” There's a major roadblock to creating personalized cancer care. Doctors need a way to target treatments to patients most likely to benefit and avoid …
Drug 
4/18/12 
Good Vibrations in Fight Against Cancer
By Case Western Reserve University
Medicine-toting nanochains slip into tumors and explode a chemotherapy drug into hard-to-reach cores of cancer, engineers and scientists at Case Western Reserve University report. In tests on rats …
Tumor 
5/5/11 
Hitting Target in Cancer Fight Now Easier with New Nanoparticle Platform, UCLA Scientists Say
By University of California - Los Angeles
The ability to use nanoparticles to deliver payloads of cancer-fighting drugs to tumors in the body could herald a fundamental change in chemotherapy treatment. But scientists are still at …
Tumors 
9/28/10 
Novel Biomarker May Predict Response to New VEGF Receptor Inhibitor
By American Association for Cancer Research
DENVER β€” Researchers believe there may be a way to predict, based on individual tumors, those patients that are more likely to respond to the investigational new drug tivozanib. …
Tumor 
10/12/10 
Fox Chase Researchers Uncover Achilles' Heel in Aggressive Breast Tumors
By Fox Chase Cancer Center
PHILADELPHIA (October 12, 2010)β€”In an unexpected twist, Fox Chase Cancer Center researchers find that the loss of a single protein, Nedd9, initially slows cancer formation but then makes the …
Features 
11/9/11 
Stanford Team Trains Computer to Evaluate Breast Cancer
By Stanford University Medical Center
Since 1928, the way breast cancer characteristics are evaluated and categorized has remained largely unchanged. It is done by hand, under a microscope. Pathologists examine the tumors visually and …
More » 
 
ScienceNewsline  |  About  |  Privacy Policy  |  Feedback  |  Mobile  |  Japanese Edition
The selection and placement of stories are determined automatically by a computer program. All contents are copyright of their owners except U.S. Government works. U.S. Government works are assumed to be in the public domain unless otherwise noted. Everything else copyright ScienceNewsline.