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Developing mathematical model driven optimized recurrent glioblastoma therapies

Award Number: R21CA263911
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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Developing mathematical model driven optimized recurrent glioblastoma therapies - Abstract High-grade gliomas, including GBM, are the most common primary brain tumors in adults. GBM treatment is not curative, and recurrent high-grade glioma (rHGG) remains fatal, despite aggressive therapy. Part of the challenge in treating glioma is its localization within the naturally immunosuppressive central nervous system. Hypofractionated stereotactic radiotherapy (HFSRT) combined with immunotherapy has shown promising antitumor activity in both preclinical and clinical studies in rHGG. Radiation induces an immunogenic cancer cell death and promotes the presentation of tumor-derived antigens to antitumor T cells, and acts synergistically with immunotherapy to enhance the immune response against tumor cells. Treatment response depends on a myriad of factors, including patient, tumor, and treatment parameters. Thus, how to best combine radiation with chemotherapy or immunotherapeutics remains unknown. Current protocols of combining radiation with different therapies are applied without considering evolutionary dynamics, and every patient's tumor develops resistance and eventually progresses. We hypothesize that evolutionary principle- guided therapies must be explored to pro-actively counteract the development of resistance. Mathematical modeling may provide the necessary tools to decipher the complex evolutionary dynamics during rHGG therapy. Trained and tested mathematical and computational algorithms can simulate a variety of treatment protocols in all possible combinations. Our innovative approach and goals are to integrate mathematical modeling to learn from past clinical studies to design a prospective clinical trial in rHGG. Using mathematical and computational algorithms to exhaustively explore different treatment protocols holds the key to improved, clinically-testable protocols, and ultimately improved rHGG outcomes. This interdisciplinary team science approach combines our expertise in neuro-oncology and radiation oncology with mathematical oncology and statistics. Moffitt Cancer Center has a rich culture of interdisciplinary research across conventional department barriers, as evidenced by a strong history of translating mathematical and computational concepts into experimental biology as well as clinical trial and practice. Here we build on robust preliminary data to harness our expertise and explore evolutionary principles-guided therapies for the first time in rHGG.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2022	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	2	11/6/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	2	5/29/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $188,644 )
2022	2022	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	001	2	7/28/2022	NON-COMPETING CONTINUATION	$188,644
2022	2021	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	1	7/25/2022	NEW	$0
														Subtotal = $188,644

Issue Date FY: 2021 ( Subtotal = $230,992 )
2021	2021	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	1	6/24/2021	NEW	$230,992
														Subtotal = $230,992

Grand Total All Awards = $419,636

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Developing mathematical model driven optimized recurrent glioblastoma therapies

Award Number: R21CA263911

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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