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Developmental and Hyperactive Ras Tumor (DHART) SPORE

Award Number: U54CA196519
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2015
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Developmental and Hyperactive Ras Tumor (DHART) SPORE - ABSTRACT – OVERALL Neurofibromatosis type 1 (NF1) is the most common inherited cancer predisposition syndrome of a group of developmental disorders that are collectively termed “Rasopathies”. Germline NF1 mutations cause neurofibromatosis type 1 (NF1), a multi-system developmental disorder that is also the most common inherited cancer predisposition syndrome. NF1 is of exceptional importance in cancer biology because it encodes a GTPase activating protein (GAP) called neurofibromin that binds to active Ras-GTP and terminates signaling by accelerating guanine nucleotide hydrolysis. Thus, NF1 inactivation and somatic cancer-associated RAS mutations result in constitutively elevated Ras-GTP levels and aberrant activation of Ras-regulated kinase effector pathways in susceptible cell lineages. A markedly increased incidence of developing specific benign and malignant tumors is a hallmark of NF1 that results in substantial morbidity and mortality that affect children, adolescents, and young adults (AYAs) in a range of tissues. Investigating NF1-associated tumors represents a unique opportunity to interrogate therapeutic responses and mechanisms of intrinsic and acquired drug resistance in cancers that are initiated by a mutation that directly enhances Ras output. Given the central importance of aberrant Ras/GAP function in human cancer, and the emerging role of somatic NF1 mutations in common sporadic malignancies, achieving the goals of this SPORE will broadly advance translational cancer research and treatment. The overall goal of this Developmental and Hyperactive Ras Tumor (DHART) SPORE is to implement effective targeted therapies for neoplasms and cancers characterized by mutations in the NF1 tumor suppressor gene (TSG) by conducting integrated, mechanistically based translational research. The DHART SPORE deploys novel organizing principles and approaches to address the key challenge of how to accelerate new therapies for uncommon (“orphan”) benign and malignant tumors across an organ spectrum with a common driver mutation. The DHART SPORE is comprised of a highly integrated group of translational scientists that are addressing central issues for implementing mechanism-based treatments for rare tumors driven by hyperactive Ras signaling in the pediatric, adolescent, and young adult (AYA) population. Across all three projects, state-of-the-art core facilities will inform the patient-oriented therapeutic and prevention aspects by delineating mutations that contribute to cancer pathogenesis, and by uncovering new biomarkers of drug response and resistance that will inform the development of “next generation” treatments. Achieving the objectives of the proposed Projects 1-3 will not only improve the outcomes of NF1 and non-NF1 patients with specific cancers but has the potential to inform new therapeutic approaches for the substantial proportion of human cancers characterized by somatic NF1 and RAS mutations that have implications for enhancing the treatment of the ~1/3rd of all cancers with somatic RAS mutations.


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: 2024 ( Subtotal = $2,208,392 )
2024	2024	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cancer Centers Support Grants	000	9	8/30/2024	NON-COMPETING CONTINUATION	$2,208,392
														Subtotal = $2,208,392

Issue Date FY: 2023 ( Subtotal = $2,139,494 )
2023	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cancer Centers Support Grants	002	8	9/6/2023	NON-COMPETING CONTINUATION	$0
2023	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cancer Centers Support Grants	001	8	8/14/2023	NON-COMPETING CONTINUATION	$2,139,494
2023	2022	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cancer Centers Support Grants	000	7	2/16/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,139,494

Issue Date FY: 2022 ( Subtotal = $2,139,494 )
2022	2022	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cancer Centers Support Grants	003	7	8/24/2022	NON-COMPETING CONTINUATION	$2,093,484
2022	2022	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cancer Centers Support Grants	004	7	9/21/2022	NON-COMPETING CONTINUATION	$46,010
2022	2021	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cancer Centers Support Grants	002	6	8/15/2022	COMPETING CONTINUATION	$0
2022	2021	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cancer Centers Support Grants	001	6	1/3/2022	COMPETING CONTINUATION	$1
2022	2019	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cancer Centers Support Grants	000	5	1/3/2022	NON-COMPETING CONTINUATION	-$1
														Subtotal = $2,139,494

Issue Date FY: 2021 ( Subtotal = $2,198,683 )
2021	2021	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cancer Centers Support Grants	000	6	9/24/2021	COMPETING CONTINUATION	$2,198,683
														Subtotal = $2,198,683

Issue Date FY: 2019 ( Subtotal = $2,124,182 )
2019	2019	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cancer Centers Support Grants	001	5	9/4/2019	NON-COMPETING CONTINUATION	$2,124,182
2019	2018	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cancer Centers Support Grants	000	4	3/1/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,124,182

Issue Date FY: 2018 ( Subtotal = $2,102,055 )
2018	2018	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cancer Centers Support Grants	000	4	9/3/2018	NON-COMPETING CONTINUATION	$2,102,055
														Subtotal = $2,102,055

Issue Date FY: 2017 ( Subtotal = $2,271,783 )
2017	2017	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cancer Centers Support Grants	000	3	8/11/2017	NON-COMPETING CONTINUATION	$2,156,782
2017	2017	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Cancer Centers Support Grants	001	3	9/21/2017	NON-COMPETING CONTINUATION	$115,001
														Subtotal = $2,271,783

Issue Date FY: 2016 ( Subtotal = $2,162,000 )
2016	2016	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Cancer Centers Support Grants	000	2	8/31/2016	NON-COMPETING CONTINUATION	$2,162,000
														Subtotal = $2,162,000

Issue Date FY: 2015 ( Subtotal = $2,384,507 )
2015	2015	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Cancer Centers Support Grants	000	1	8/26/2015	NEW	$2,185,000
2015	2015	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Cancer Centers Support Grants	001	1	9/2/2015	NEW	$199,507
														Subtotal = $2,384,507

Grand Total All Awards = $19,730,590

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Developmental and Hyperactive Ras Tumor (DHART) SPORE

Award Number: U54CA196519

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/01/2015

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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