ALBANY, N.Y. — Research conducted at Albany Medical College could transform treatment and expand lifespans for people with glioblastoma, an aggressive brain tumor and one of the most deadly forms of cancer.
“Our results show a potential new way to stop cancer cells from proliferating or migrating to other areas of the brain, essentially ‘freezing’ the tumor in place,” said Alexander A. Mongin, Ph.D., associate professor in the Department of Neuroscience and Experimental Therapeutics (DNET) at Albany Medical College, who led the study.
The results were published recently in the journal Frontiers in Oncology.
Glioblastoma (GBM) is the most common malignant primary brain tumor in adults – that is, cancer that begins within the brain – with approximately 14,000 new diagnoses each year. Senator John McCain was diagnosed with GBM in 2017.
The current standard-of-care includes surgery to remove as much of the tumor as possible, chemotherapy and radiation. However, treatment options are limited because the cancer cells rapidly disperse to healthy parts of the brain and quickly develop resistance to chemotherapy. As a result, tumors often recur even after surgery and the average life expectancy is only one year.
The Albany Med team, which included basic science researchers and physician-scientists, focused on the ion channel protein LRRC8A, which is believed to facilitate the rapid growth of GBM cells. Using a gene-specific RNAi approach to inhibit specific molecules, they eliminated the expression of LRRC8A in human cancer tissue samples.
The researchers found that when LRRC8A was blocked, cancer cells didn’t grow as fast. Surprisingly, blocking LRRC8A was more effective in slowing cancer growth than currently used chemotherapeutic agents.
Importantly, targeting LRRC8A enhanced the effect of chemotherapy: when blocking LRRC8A was combined with temozolomide and carmustine, two commonly used chemotherapy drugs, treatment was three times more effective than chemotherapeutic agents acting alone.
“There’s a long road between initial discovery and viable treatment, but the findings from this study indicate a promising new target for the treatment of GBM, alone or in combination with the current standard-of-care,” said Dr. Mongin. “GBM is so resistant to all current treatments that any agent allowing to increase patients’ life expectancy would be a big deal,” he added.
In addition to Dr. Mongin, the researchers leading the study were Albany Med neurosurgeon Sebastian Rubino, M.D., Albany Medical College graduate student Alexandra L. Schober, Ph.D. and Martin D. Bach, a visiting student from the University of Copenhagen.
Dr. Rubino, who has seen firsthand the course of this disease in his patients, noted that ideally, they hope to eradicate diseases like GBM; at the least, they hope to make them better tolerated. “Our goal is to make this deadly disease a chronic one that can be lived with,” he said. “Partnerships like this between clinicians and basic science researchers are paramount in making those advances and finding new cures for brain disorders.”
Titled “Downregulation of Leucine-Rich Repeat-Containing 8A Limits Proliferation and Increases Sensitivity of Glioblastoma to Temozolomide and Carmustine,” the full study can be read online on Frontiers in Oncology’s site at: https://www.frontiersin.org/articles/10.3389/fonc.2018.00142/full.
This research was supported in part by the National Institutes of Health, with translational funds provided by Albany Medical College.
Albany Medical Center, northeastern New York’s only academic health sciences center, is one of the largest private employers in the Capital Region. It incorporates the 734-bed Albany Medical Center Hospital, which offers the widest range of medical and surgical services in the region, and the Albany Medical College, which trains the next generation of doctors, scientists and other healthcare professionals, and also includes a biomedical research enterprise and the region’s largest physicians practice with more than 450 doctors. Albany Med is affiliated with Columbia Memorial Health and Saratoga Hospital to provide the largest locally governed health system in the region. Combined, these three hospitals offer nearly 1,100 beds and outpatient locations throughout the Capital Region. Albany Medical Center works with dozens of community partners to improve the region’s health and quality of life. For more information: www.amc.edu or www.facebook.com/albanymedicalcenter.
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