Durham, NC – Researchers have discovered a protein that stops stem cells from forming the most common and lethal type of brain tumor. At the same time, they located a trigger that activates this protein — metformin, a low-cost drug widely prescribed to treat type 2 diabetes.
The findings published today in STEM CELLS Translational Medicine suggest a new treatment path for glioblastoma, a highly aggressive, deadly malignancy. The median survival time for adults diagnosed with glioblastoma is just one to two years.
“Researchers have been seeking a way to control the initiating cancer stem cell population, considered key to realizing the long-term survival of these patients,” said Drs. Chifumi Kitanaka and Atsushi Sato, who led the team of scientists from Yamagata University in Japan on the study. “Previous reports have underscored the idea that differentiation therapy, which involves controlling stem cells’ development into particular cells or tissue, is a promising approach to depleting the tumor-initiating cells in glioblastomas and in preventing their recurrence.”
In an earlier study, the Yamagata team had shown that a protein called FOXO3 promotes the differentiation of stem-like cells within human gliomas into non-cancerous cells in vitro. FOX (Forkhead box) proteins are important in regulating the expression of genes involved in cell growth, proliferation, differentiation and longevity. Undifferentiated tumor cells are associated with having much high tumor-initiating potential than differentiated cells.
The scientists next went in search of a therapeutic activator of FOXO3 and came up with metformin. This drug is widely used to control the amount of glucose in the blood by decreasing the amounts of glucose absorbed from food and produced by the liver, while at the same time increasing the body's response to insulin.
“In mice studies, the administration of metformin had several benefits. It depleted the self-renewing and tumor-initiating cell population within established tumors, inhibited tumor formation by stem-like glioma-initiating cells in the brain and provided substantial survival benefit,” Dr. Sato said.
Dr. Kitanaka added, “Combined with the fact that metformin has already been used safely in the clinic and that it efficiently penetrates the blood-brain barrier and accumulates in the brain, our findings suggest that metformin is a strong candidate for clinical use as a cancer stem/initiating cell-targeting drug against glioblastoma as well as against some other human cancers.”
“This research team has established a novel link between glucose metabolism and cancer stem cells,” said Anthony Atala, MD, editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “Their finding suggests a potential new line of clinical research directed at this deadly form of brain cancer.”
The full article, “Glioma-initiating cell elimination by metformin activation of FOXO3 via AMPK,” can be accessed at http://www.stemcellstm.com.
About STEM CELLS Translational Medicine:
STEM CELLS TRANSLATIONAL MEDICINE (SCTM), published by AlphaMed Press, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.
About AlphaMed Press:
Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes two other internationally renowned peer-reviewed journals: STEM CELLS® (www.StemCells.com), celebrating its 30th anniversary in 2012, is the world's first journal devoted to this fast paced field of research. The Oncologist® (www.TheOncologist.com), also a monthly peer-reviewed publication, entering its 18th year, is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. All three journals are premier periodicals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines.