The new generation of genetically-engineered mouse models (GEMs) holds promise for helping cancer prevention researchers refine and speed up testing of potential preventive agents. These mice are programmed to develop specific types of cancer in ways that mimic human cancer. That may make it easier for scientists, using sophisticated imaging technologies, to gauge the effects of cancer preventive substances.
This summer, NCI will convene a "think tank" of 15-18 invited experts from the fields of early intervention, prevention, and prevention screening, as well as from the NCI Mouse Models of Human Cancers Consortium (MMHCC), to develop research plans that fully explore the promise of GEMs.
"The meeting will bring together a cadre of scientists from diverse fields," noted Dr. Cory Abate-Shen, professor with the Center for Advanced Biotechnology and Medicine, UMDNJ-Robert Wood Johnson Medical School. "This will facilitate a dialogue, which is critical. Working together, we can develop ideas for studies that will enable us to assess the value of these newer mouse models for cancer prevention."
In NCI's Division of Cancer Prevention (DCP), the Chemopreventive Agent Development Research Group, as well as many NCI funded investigators, have published more than a hundred studies using GEMs for the past decade. These studies in multiple organ systems have identified a variety of agents that have progressed to human clinical trials, including nonsteroidal anti-inflammatory drugs (NSAIDS), nitric-oxide-releasing NSAIDS, glucocorticoids, retinoid X receptor agonists, aromatase inhibitors, tazarotene, and ACAPHA (a mixture of Chinese herbs). However, more recently developed GEM models may be especially well suited to future prevention studies.
The upcoming think tank will address several key questions related to this, explained NCI's Dr. Cheryl Marks, who administers the MMHCC. "The intent of the meeting is to identify the principal challenges facing early intervention and prevention, define the future goals, identify limitations of mouse models and strategies to overcome those limitations, and discuss how to effectively use these newer mouse models for cancer prevention."
Until now, research with GEMs and other mouse models in the MMHCC has focused more on their applicability for safe and effective treatments for cancer rather than on prevention.
Last year in Toxicologic Pathology, participants from a previous MMHCC workshop reported on precancer research. "The scientific community suddenly possesses a wealth of precancers available for study in a variety of organ systems," they wrote. "Since most of the GEMs have been constructed to test oncogenes or tumor suppressor genes known to be involved in human cancer, these precancers should become primary targets for understanding, treatment, and prevention and ideal representations of processes occurring in human precancers."
Dr. Abate-Shen noted that human clinical trials for cancer preventive agents can take many years before delivering definitive results, whether positive or negative, about the drug or nutritional supplement. "Our goal would be to test agents in these newer mouse models to understand their mechanism of action and to guide clinical studies," she said.