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"Modulating Cell Invasion as a Strategy to Treat Brain Tumors"
Ravi Bellamkonda, PhD
Professor, Wallace H. Coulter Department of Biomedical Engineering
Associate Vice President for Research
Brain tumors are the most common solid tumors in children. Glioblastoma multiforme in adults has a very poor prognosis, with a mean survival time of 9 months after diagnosis. Poor outcomes after treating brain tumors clinically with usual arsenal of surgery, radiation and chemotherapy are often attributed to the tumors invasive character. The ‘moving target’ makes surgery, radiation and chemotherapy challenging.
Our laboratory is interested in nano and sub-micron scale technologies that modulate the invasive characteristics of brain tumors to enhance therapeutic outcomes. First, in collaboration with Prof. Jack Arbiser’s lab at Emory, we have developed a novel nanocarriers system that halts the spread of invasive brain tumors in rodents. Not only have we demonstrated that we are able to halt brain tumor invasiveness in vivo, we suggest that a combination therapy of our nano-carriers and clinically approved chemotherapy increases survival to 200+days in rodents. Thus, by stopping tumor migration, we demonstrate increased efficacy of ‘conventional’ therapy.
However, there remain tumors of the head and neck region that are challenging to treat. In particular, meduloblastomas and some brain stem tumors tend to migrate along white matter tracts and invade other regions of the brain. To exploit the property of brain tumors to migrate along convex, topographical cues we have designed nanofiber based films that help ‘exvade’ tumors to the brain surface where they are collected by a hydrogel sink where they die.
Lastly, penetration of solid tissues by nano-scale carriers remains poor due to their relatively large sizes. We are currently exploring novel methods to increase the penetration of nanocarriers into solid tumors so a better distribution of chemotherapeutic in the tumor can be achieved.
This work was funded by National Cancer Institute, Ian’s Friends Foundation, CHOA and the Georgia Cancer Coalition. Other critical contributors to this work include: Jenny Munson, Anjana Jain, Barun Brahma, several Bellamkonda lab undergraduate students and Jack Arbiser.
About the Integrated Cancer Research Center:
Georgia Tech has been a leader in the development of collaborative approaches to both cancer diagnostics and therapeutics. The mission of the Integrated Cancer Research Center is to facilitate integration of the diversity of technological, computational, scientific and medical expertise at Georgia Tech and partner institutions in a coordinated effort to develop improved cancer diagnostics and therapeutics.