National Cancer Institute grants support efforts to understand how fluid flow drives deadly brain cancer

(Press-News.org) Jennifer Munson, a cancer researcher at Virginia Tech's Fralin Biomedical Research Institute at VTC, has been awarded two new National Institutes of Health grants to advance greater understanding and improved treatment of a deadly brain cancer.

While the grants from the National Cancer Institute fund different projects, both involve identifying how the movement of fluid surrounding tumor cells contributes to the spread of glioblastoma, a deadly brain tumor, into neighboring brain areas, allowing the cancer to return after surgery or radiation.

Munson and her team are identifying how liquid called interstitial fluid moves between cells and possibly contributes to the spread of tumor cells into neighboring brain areas, allowing the cancer to return and spread after treatment with surgery or radiation.

One of the grants, a five-year, $2.6 million award, aims to study how fluid flow changes with treatment, and how focused ultrasound can be leveraged to better target and distribute therapy.

The other grant, a two-year, $411,000 award, supports a project to build a novel model of fluid-filled spaces that surround vessels in the brain and how they behave in health and during cancer treatment.

“There are no effective therapies for glioblastoma, one of the most common types of adult primary brain tumors and one of the most lethal human cancers,” said Munson, a professor at the Fralin Biomedical Research Institute. “New approaches to understanding how this cancer invades tissues and recurs, and better treatments and targeted methods, are desperately needed.”

Mapping flow in the brain With the two-year grant, Munson is teaming up with Malisa Sarntinoranont, professor of mechanical engineering at the University of Florida. The collaboration will combine the Munson lab’s expertise in fluid flow and imaging with Sarntinoranont’s advanced computational modeling to develop the first whole-brain model of flow in the fluid-filled spaces around certain arteries.

The goal is to gain insight into how underlying structures in the brain may contribute to flow the transport of cancer cells during tumor growth.

The study will employ advanced MRI techniques to generate dynamic imaging of fluid flow in healthy brains and preclinical models with tumors. The team will generate detailed maps of fluid flow and use the maps to build computational models of flow in tumor development in the whole brain.

The model can then be used to examine differences in flow during tumor development, and to test the impacts of the anti-inflammatory and commonly administered drug dexamethasone on glioblastoma tumor progression.

Fluid flow and focused ultrasound With the other grant, Munson proposes to leverage interstitial fluid flow in a novel way, to target, assess, and plan individual patient-specific glioblastoma treatment.

Munson’s lab has previously developed imaging and analysis methods that predict where a tumor is likely to reappear after treatment.

Cheng-Chia “Fred” Wu, a radiation oncologist and cancer researcher at the Fralin Biomedical Research Institute, is using focus ultrasound to transiently open the blood brain barrier, which can keep cancer drugs from reaching tumors. Wu has labs in Roanoke and at the Children’s National Research & Innovation Campus in Washington, D.C.

The labs will use mapping to identify the best focused ultrasound targets and work with Associate Professor Eli Vlaisavljevich and Research Associate Professor Adam Maxwell of Virginia Tech’s Department of Biomedical Engineering and Mechanics to develop a more precise focused ultrasound system.

The study also aims to determine how fluid flow is affected by different therapies. It could serve as a biomarker for therapeutic efficacy. In addition, the researchers will work with Russell Rockne, associate professor at the City of Hope comprehensive cancer care center in California, to develop mathematical models to predict tumor progression and drug distribution in light of changes.

“This coupling of precision identification with precision equipment is a major translational leap for our research,” said Munson, who also is director of the FBRI’s Cancer Research Center — Roanoke. “By the end of our project, we expect to have a tool set and understanding of how fluid flow changes and predicts therapeutic responses and progression in this devastating and treatment-resistant cancer.”

Munson also holds an appointment in the Department of Biomedical Engineering and Mechanics in Virginia Tech’s College of Engineering.

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