Awarding Grants to Research Projects Focused on Brain Tumor Treatment

"It is my long-term goal to become an independent clinical investigator and leader in the study of neurological cancer. Receiving funding from the American Brain Tumor Association and The Southeastern Brain Tumor Association allowed me to take concrete formative steps toward this goal and further inspired me to continue pursuing this work in my career. During my time as an ABTA-funded medical student investigator, I was able to work with and learn from leaders in the field of neurological cancer research on a cutting-edge project at a top institution. I learned skills needed to develop an impactful project proposal, submit application for funding, execute a project in an efficient manner, and collaborate across institutions. The laboratory techniques honed and collaborative mentoring relationships established during this work has bolstered my confidence and passion and prepared me for the crucial next steps in my career progression. As a direct result of this experience, I am prepared to complete future applications for funding, develop and lead independent research projects, work collaboratively across institutions, design and execute translational research, and mentor others. Thanks to the funded opportunity from ABTA, I feel not only inspired but empowered to continue to advocate for patients and work to discover new treatments for patients with neurological cancers."

"Glioblastoma is the most common and aggressive primary brain tumor in adults, with a median survival of 14 months after diagnosis. Tumor recurrence is nearly universal, due to a combination of treatment resistance, tumor invasiveness, and communication with other cells in the brain. It has been found, in particular, that glioblastoma are more aggressive when they grow in neurogenic regions of the brain that normally give rise to healthy stem cells. Preliminary evidence from Dr. Hugo Guerrero-Cazares’ lab indicated that communication between brain tumor cells and stem cells via extracellular vesicles induces a pro-cancer phenotype in neural stem cells. My project explored the role of these vesicles by intercepting their mechanism using a drug called chloramidine, which blocks their release. If the use of chloramidine successfully blocks extracellular communication by glioblastoma cells and results in a decreased cancer malignancy, this would be a novel therapeutic pathway for treating patients with malignant brain cancer. During my time working on this project, we were able to determine concentrations of this drug that were non-toxic to cells, a foundational step for further experiments exploring downstream effects of the drug. Additionally, we began to elucidate a trend in the drug’s ability to stop the release of extracellular vesicles. Experiments in the project are ongoing and seek to determine working concentrations and effects of this drug on cancer progression."

His 2016 SBTF awarded grant, "Investigating the role of N-cadherin in the therapeutic resistance of Glioblastoma," provided results which resulted in submission to the Department of Defense and subsequent award of a two-year $664,000 DOD grant issued in February of 2018.

"The grant support from SBTF has been extremely essential and helpful to our research. We are now ready to submit the first manuscript reporting our findings, and more importantly, we also expect to receive a R01 grant from NIH which will allow us to advance our study significantly. None of these would have been possible without the generous support from the SBTF."

Dr. Thompson's project resulted in exciting findings: research reflects a commonly used steroid, dexamethasone, plus a drug efflux inhibitor tariquidar can enhance the efficacy of the targeted chemotherapeutic agent, dastinib to treat DIPG.

Published in the Journal of Neurosurgery June 2019 issue: "ABC transporter Inhibition Plus Dexamethasone enhances the efficacy of convection enhanced delivery in H3.3K27M Mutant DIPG"

"Your contributions, belief, and support of our work have most definitely allowed us to generate a foundation for gliomagenesis and how the mutations we study contribute to the tumors.  We hope to share with you even more exciting ideas in this next application, which we believe, will be fundamental to future therapies.  The proposal will be dealing with an immunotherapeutic approach to targeting the most common mutation identified in gliomas."

Therapeutic Targeting of Id1 in Glioblastomas

Aim 1.1: Presented at 2015 AACR mtg, expect to submit manuscript in 1-2 months. In planning stages for preparing an RO1 grant proposal to NIH.

Aim 1.2: Unable to demonstrate a significant capacity, will not pursue this avenue of research.

Aim 2: Will continue to test the efficacy, predict the drug will cross blood brain barrier. Experiments ongoing, expect the work will be combined with work from Aim 1.1

This research proved to be an important stepping stone toward clinical trials using polio virus.

Interim report- Phase 1 of clinical trial in patients with recurrent GBM is progressing as planned, remarkable durable, complete clinical and radio-graphic responses in the first patients (as reported in application) are holding up. Currently observing similar responses in further patients.

This research was granted "Breakthrough Status" in 2016 which indicated the FDA wanted to speed up the research and saw great potential in the science.

This research was featured in a 60 Minutes story in March 2015. A follow up interview was held in May of 2016.

As of December 2019, this research is in Phase III Trials at several institutions and is receiving favorable results.

"We made significant headway; now have critical mass of data supporting the role of the antiviral immune response in oncolytic viral anti-tumor activity; applying for federal funding using this data. The SBTF funds allowed researcher to establish an animal model that permits examination of the immune mediated anti-tumor response independent of other viral anti-tumor effects."

"We did indeed publish a manuscript on the project that was supported by our SBTF grant in the journal Cancer Research, and the SBTF support is acknowledged in the publication. Regarding our work on the drug verteporfin, we recently wrapped up our early phase 0/1 trial of verteporfin in human GBM patients and are now trying to publish that research."

"R01 funding on the role of PPM1D in medulloblastoma, funded 2012-2018. This funding was possible in part due to seed funding from SBTF."

Continued studies and submissions which resulted in 5 year RO1 grant from NIH of approx $1.6M

"Research initially funded (in part) by SBTF in 2009 led to additional studies. An immunotoxin from the initial study, conducted by Vidya Chandramohan, Ph.D., Preston Robert Tisch Brain Tumor Center, is now being evaluated in a Phase I/II clinical trial for recurrent Glioblastoma patients. https://www.clinicaltrials.gov/ct2/show/NCT02303678."

"The Brain Tumor Nanotechnology Laboratory has translated the use of the magnetic nano particles proposed in the SBTF grant over four years ago to a canine clinical trial at the University of Georgia.  Canines with spontaneous brain tumors are being treated with the nano particles our laboratory synthesizes for safety and efficacy testing. We had promising results and hope to take this to humans soon. Manuscript has resulted from research."

"Another victory for cancer researchers. This project which reduces tumor thrombosis by regulating the tissue factor pathway yielded findings which showed when tumor suppressor p14ARF is lost during tumor progression, this leads to the cocomitant loss of a factor that normally prevents coagulation". The advances mean anti-thrombotic agents might have anti-tumor effects Next step is to test the hypothesis in an animal model to see if this approach has promise for development of a novel therapeutic approach for patients with malignant brain tumors."