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Advancing Cancer Therapy through Groundbreaking Research in Radiation Biology

Award Number: R35CA197616
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/16/2016
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Advancing Cancer Therapy through Groundbreaking Research in Radiation Biology - PROJECT SUMMARY/ABSTRACT Radiation therapy is utilized to treat approximately half of all cancer patients. For some patients, radiation therapy can achieve local tumor control and cure. For other patients, radiation therapy palliates symptoms and alleviates suffering. However, radiation therapy can also cause acute toxicity and late effects that diminish quality of life. The goal of our research program is to widen the therapeutic window of radiation therapy by dissecting mechanisms of normal tissue radiation injury and tumor response to radiotherapy. As I am a sarcoma radiation oncologist, my research group not only studies sarcoma response to radiation therapy, but also sarcoma development and metastasis. During the prior funding period, we adapted CRISPR/Cas9 technology to develop novel genetically engineered mouse models of sarcoma that facilitated lineage tracing of sarcoma clones during tumor progression. This approach identified novel regulators of metastasis, which are potential targets for new cancer therapies. We also used new mouse and in vitro models to discover a novel mechanism for the exquisite radiosensitivity of myxoid liposarcoma: DNA-damage induced phosphorylation of a prion-like domain in the FUS-CHOP fusion protein disrupts interactions with chromatin remodeling complexes that are required for tumor maintenance. We initiated new projects with a novel sarcoma model with high tumor mutation burden that revealed tumor-intrinsic and immune-mediated mechanisms of response and resistance to radiotherapy and immunotherapy. Our findings provided the rationale for a randomized clinical trial in sarcoma patients testing radiation therapy with immune checkpoint inhibition. We also used our genetically engineered mice to uncover mechanisms regulating acute toxicity and late effects of radiation, such as radiation carcinogenesis. Our proposed research will build on the success of our recent work. We will use innovative model systems and sophisticated approaches to make discoveries in three broad areas: 1. Response of sarcomas to radiotherapy 2. Response and resistance of sarcomas to radiation and immunotherapy 3. Normal tissue injury from radiation The knowledge gained from the proposed studies will not only deepen our understanding of radiation and sarcoma biology, but will also inform the design of future clinical trials that aim to widen the therapeutic ratio of radiation therapy to improve the outcome for patients with sarcomas and other cancers.


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 = $829,136 )
2025	2025	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Cancer Treatment Research	000	11	8/29/2025	NON-COMPETING CONTINUATION	$829,136
														Subtotal = $829,136

Issue Date FY: 2024 ( Subtotal = $382,796 )
2024	2024	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Cancer Treatment Research	002	10	8/19/2024	NON-COMPETING CONTINUATION	$382,796
2024	2023	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Cancer Treatment Research	001	9	5/2/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$437,331
2024	2022	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cancer Treatment Research	000	8	5/2/2024	COMPETING CONTINUATION	-$437,331
														Subtotal = $382,796

Issue Date FY: 2023 ( Subtotal = $902,223 )
2023	2023	HEALTH RESEARCH, INC.	ELM & CARLTON ST	BUFFALO	NY	14263	ERIE	USA	Cancer Treatment Research	003	9	9/8/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$902,223
2023	2022	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cancer Treatment Research	000	7	8/29/2023	NON-COMPETING CONTINUATION	-$270,112
2023	2022	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cancer Treatment Research	002	8	9/8/2023	COMPETING CONTINUATION	$0
2023	2022	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cancer Treatment Research	001	8	8/29/2023	COMPETING CONTINUATION	$270,112
														Subtotal = $902,223

Issue Date FY: 2022 ( Subtotal = $1,874,586 )
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	000	7	12/16/2021	NON-COMPETING CONTINUATION	$848,525
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	003	8	9/22/2022	COMPETING CONTINUATION	$950,637
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	001	7	5/24/2022	NON-COMPETING CONTINUATION	$75,424
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	002	7	9/14/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,874,586

Issue Date FY: 2021 ( Subtotal = $942,807 )
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	001	6	12/31/2020	NON-COMPETING CONTINUATION	$895,975
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	002	6	1/20/2021	NON-COMPETING CONTINUATION	$46,832
2021	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	003	5	2/1/2021	NON-COMPETING CONTINUATION	$0
2021	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	000	5	12/30/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $942,807

Issue Date FY: 2020 ( Subtotal = $1,016,247 )
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	000	5	12/3/2019	NON-COMPETING CONTINUATION	$914,607
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	001	5	1/14/2020	NON-COMPETING CONTINUATION	$101,640
2020	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	003	4	4/14/2020	SUPPLEMENT FOR EXPANSION	$0
2020	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	002	4	4/14/2020	NON-COMPETING CONTINUATION	$0
2020	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	004	3	4/22/2020	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $1,016,247

Issue Date FY: 2019 ( Subtotal = $985,728 )
2019	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	001	4	12/19/2018	SUPPLEMENT FOR EXPANSION	$71,206
2019	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	000	4	12/7/2018	NON-COMPETING CONTINUATION	$914,522
														Subtotal = $985,728

Issue Date FY: 2018 ( Subtotal = $997,732 )
2018	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	001	3	5/23/2018	NON-COMPETING CONTINUATION	$94,282
2018	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	000	3	11/23/2017	NON-COMPETING CONTINUATION	$848,525
2018	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	002	3	6/28/2018	SUPPLEMENT FOR EXPANSION	$54,925
														Subtotal = $997,732

Issue Date FY: 2017 ( Subtotal = $942,807 )
2017	2017	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	001	2	6/8/2017	NON-COMPETING CONTINUATION	$94,282
2017	2017	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	000	2	12/1/2016	NON-COMPETING CONTINUATION	$848,525
														Subtotal = $942,807

Issue Date FY: 2016 ( Subtotal = $942,807 )
2016	2016	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Cancer Treatment Research	000	1	12/30/2015	NEW	$942,807
														Subtotal = $942,807

Grand Total All Awards = $9,816,869

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Advancing Cancer Therapy through Groundbreaking Research in Radiation Biology

Award Number: R35CA197616

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/16/2016

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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