May 3, 2013 | by Nicole White
Triple-negative breast cancer is both aggressive and tough to fight with existing therapies, a combination that often results in the disease's spread; in fact, most deaths related to this form of cancer occur due to metastases. New City of Hope research is targeting these metastases specifically.
Building on a platform developed at City of Hope by Karen Aboody, M.D., Rachael Mooney, Ph.D., a postdoctoral CIRM Scholar and a fellow in Aboody's laboratory, hopes to use stem cells to deliver tiny packages of chemotherapy to breast cancer-related metastases.
Aboody’s platform involves neural stem cells that naturally home in on cancer sites in the body. These cells are modified to secrete an enzyme that activates a prodrug – a benign substance – to become a powerful cancer-killing agent locally at the tumor sites.
Mooney is collaborating with Jacob Berlin, Ph.D., to adapt this platform into a cancer-targeting delivery system for nanoparticles, essentially plastic containers 10,000 times smaller than the width of a single human hair. The “containers” are filled with chemotherapy drugs and attached to the neural stem cells, which then move toward metastatic tumor sites – even crossing the blood-brain barrier to reach tumor metastases in the brain. Upon reaching the tumor site, the “container” is triggered to release the tumor-toxic drugs.
Early work on this approach has been so promising that Mooney recently won a prestigious two-year postdoctoral cancer research fellowship awarded by the Ladies Auxiliary to the Veterans of Foreign Wars of the United States to focus specifically on breast cancer metastases.
“Cancer cells are very dynamic and elusive, mutating so quickly our current drugs cannot find or fight them,” said Mooney, who earned her doctorate from the University of Colorado at Boulder and is studying business at Keck Graduate Institute. “By using a living cell to deliver drugs, it can respond to environmental signals in the body – like inflammation – to track the tumors.”
Mooney’s work focuses specifically on metastases resulting from triple-negative breast cancer, so named because these cancers do not produce any of the three main proteins targeted by many drugs used to fight breast cancer, making them very difficult to combat. About 15 percent of breast cancers are of this variety, which is why researchers are determined to discover new weapons to combat these cancers.
Aboody and colleagues have already shown that the neural stem cell platform is effective for treating glioma, a rapidly growing type of brain tumor in preclinical models. They have just completed a first-in-human safety/feasibility study for recurrent glioma patients at City of Hope.
Mooney initially started investigating this potential avenue, combining tumor-finding stem cells with drug filled nanoparticles, for fighting brain tumors with a post-doctoral scholarship from the California Institute for Regenerative Medicine (CIRM).