Durham, NC (PRWEB) September 19, 2012
Genetically engineered mouse models appear to be the most accurate preclinical predictor of how cancer-fighting drugs are delivered to melanoma patients, a new study has found.
The study, led by UNC-Chapel Hill researchers along with colleagues in the Research Triangle Park, Pittsburgh and Austria, was published online today in The Oncologist. It tested how four different types of mouse models predict the delivery of carboplatin, a commonly used anticancer drug, to melanoma tumors in patients.
Before a new cancer drug can be offered in clinical trials, it is tested in mice or other preclinical models to evaluate how it acts on a living organism. Key parts of this process include pharmacokinetic and pharmacodynamic studies, which 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.
“Because carboplatin is widely used, we have good data on how the drug works pharmacokinetically 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,” said study co-author 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. “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.”
Traditional anticancer drug development has relied on xenografts, or the transplanting of human cancer cell lines in immune-compromised mice, but the usefulness of this practice has recently been questioned. This study marks the first direct, comprehensive comparison of the efficacy of xenograft models, genetically engineered mouse models (GEMMs), and two types of orthotopic syngeneic transplants (OSTs), where tumor cells are transplanted to the appropriate part of the body.
“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,” said study co-author Ned Sharpless, MD, Wellcome Distinguished Professor of Cancer Research and Associate Director for Translational Research at UNC Lineberger. “This study provides valuable validation that genetically engineered models can help us accomplish this objective.”
Researchers examined plasma and tumor pharmacokinetic (PK) parameters – a critical factor influencing the predictability of rodent tumor models – in the four models and compared those parameters to human patients. Unlike xenografts and OSTs, which transplant active human or rodent cancer cells into an animal, the GEMM approach allows tumors to develop on their own over time in the mice, providing the most relatable process to how they develop in humans.
“This study could advance the pharmacokinetic testing of other anticancer drugs, and on various types of cancer – and it’s especially important for testing small-molecule cancer drugs in an effort to minimize side effects and improve safety,” said Martin Murphy, Jr., PhD, DMedSc, Executive Editor of The Oncologist. “It’s the type of impactful research that The Oncologist highlights as leading to better cancer patient care.”
The research received support by the UNC Lineberger Comprehensive Cancer Center Mouse Phase I Unit, grants from Golfers Against Cancer, the National Institutes of Health (ES014635 and CA141576), the UNC Lineberger University Cancer Research Fund and the American Cancer Society.