The Georgia Institute of Technology has received a EUREKA grant from the National Institutes of Health (NIH) to design a new way to treat invasive brain tumors by capturing the migrating cells that spread the disease. The EUREKA — Exceptional, Unconventional Research Enabling Knowledge Acceleration — program helps scientists test new, unconventional ideas or tackle major methodological or technical challenges.
The research team plans to develop a system that will excavate brain tumor cells by directing them away from their location in the interior of the brain to a more external location where they can be removed or killed. Nanofiber-based polymer thin films coated with biochemical cues will be aligned in the brain to provide a corridor for tumor cells to follow to a gel-based ‘sink’ where they will be captured and safely removed or encouraged to die through chemical signaling.
“We believe this is the first attempt to exploit the invasive, migrating properties of brain tumors by engineering a path for the tumors to move away from the primary site to a location where treatment can occur,” said lead investigator Ravi Bellamkonda, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
Collaborating with Bellamkonda on this project are Tobey MacDonald, director of the pediatric neuro-oncology program at the Aflac Cancer Center and Blood Disorders Service of Children’s Healthcare of Atlanta and an associate professor of pediatrics at the Emory University School of Medicine; and Barun Brahma, a pediatric neurosurgeon at Children’s Healthcare of Atlanta. The initial partnership between the researchers began with seed funding from the Georgia Cancer Coalition and Ian’s Friends Foundation.
The National Cancer Institute is providing more than $1 million for the EUREKA grant. For the project, Bellamkonda, MacDonald and Brahma are focusing on treating medulloblastomas — highly malignant brain tumors that account for more than 20 percent of pediatric brain tumors.
“Medulloblastoma is the most common malignant brain tumor we see in children, but unfortunately the five-year survival rates for children with this cancer only range from 50 to 70 percent and the majority of survivors have a significantly reduced quality of life as a result of treatment-related toxicities,” said MacDonald, who is also a Georgia Cancer Coalition Distinguished Scholar. “An increasing number of survivors are also at risk for developing secondary malignancies as a result of the treatment we now administer. Clearly we have to do a much better job at treating these tumors; however, improving survival while reducing the toxic effects of treatment will require a highly innovative approach.”
Medulloblastoma treatment currently involves surgery followed by radiation therapy to the entire brain and spine and up to one year of intensive intravenous chemotherapy. However, radiation is often delayed or omitted altogether in young children due to its debilitating long-term side effects on the developing central nervous system.
These changes to the timing of radiation administration can adversely impact survival. And while surgery is a mainstay of treatment, it too can cause a significant loss of cognitive and neurological function due to the critical areas of the brain that may be involved by the tumor’s spread but require an extensive surgical area to remove as much of the tumor as possible.
This EUREKA grant aims to address the urgent need to develop therapies to safely treat invasive medulloblastomas in children.
“Our plan is to deliver the tumor to the drug — by directing tumor cells to a specially engineered gel that can be removed or designed to kill the cells — rather than the current strategy of delivering the drug to the tumor, which is problematic due to the irregular vasculature and poor diffusivity of the tumor tissue,” explained Bellamkonda, who is also a Georgia Cancer Coalition Distinguished Scholar.
The researchers plan to design a polymer thin film system that will include topographical and biochemical cues similar to those that guide the initial brain tumor invasion. The thin films will be rolled up and deployed with minimally invasive catheters. Because neural tissue will not be suctioned and the films are very thin, there should be minimal tissue and tumor disruption.
The films will also be non-toxic to the patient because they will be engineered with biocompatible, stable polymers. In previous studies, the polymers have been implanted in the nervous systems of small animals for more than 16 weeks with no adverse tissue reactions.
“This research represents a radical approach to treating invasive tumors that is based on the universal properties and mechanics of cell motility and the migration characteristic of metastasis, regardless of the molecular and genetic origins of the tumor,” added Bellamkonda.
If successful, this approach would identify a new and innovative way to treat pediatric medulloblastomas and has the potential to open a new avenue for the treatment of other invasive solid tumors, such as brain stem tumors. These cancers are incurable because they are located in an inoperable region and/or they are resistant or inaccessible to the delivery of chemotherapy agents.
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