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Mayo Clinic Hepatobiliary SPORE

Award Number: P50CA210964
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/10/2018
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Mayo Clinic Hepatobiliary SPORE - OVERALL – PROJECT SUMMARY This is a renewal of the NCI-supported Mayo Clinic SPORE in Hepatobiliary Cancers (HBC), with a foundation built upon innovative translational science and utilizing state-of-the-art approaches to understand and treat liver cancers; these are the second leading cause of cancer deaths in the country. The breadth of the projects spans hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and pediatric/young adult fibrolamellar (FLC). Three unique translational projects promise significant steps forward, supported by three well-constructed and responsive cores. Additionally, robust Developmental Research and Career Enhancement Programs continue to identify and support talented HBC-investigators Ongoing support from the Mayo Foundation and Mayo Clinic Comprehensive Cancer Center benefit these components by enabling integrated resources, skilled staff, and leadership guidance to ensure success. The approach remains comprehensive, milestone focused, and patient centered. For example, the completion of former Project 3 has led to a novel first-in- class compound that has advanced to clinical trial. Three projects have developed successfully into innovative renewal pro- jects that utilize novel approaches of immunotherapeutics, computational biology, and chemical genomics. The translational projects in this renewal proposal investigate HBC biology to enhance therapeutic response, building on recent, promising clinical and preclinical advances, summarized below. Diagnostics and drug repurposing for FLC: Project 1 demonstrates 1) differential therapeutic sensitivity of FLC but with 2) variability in patient responsiveness, and now extends into a novel functional approach to precision medicine by 3) defining therapeutics that affect FLC cell viability, while also 4) developing blood- and urine-based biomarkers for tumor burden. Targeting yes- associated protein (YAP), transcriptional enhanced associate domain (TEAD) oncogenic signaling, and therapeutic resistance in CCA: developed from studies defining alternative mechanisms activating this “undruggable” target (YAP) in CCA, Project 2 will 1) leverage a novel inhibitor in preclinical models and 2) test clinical efficacy in a clinical trial. Reversal of the immune suppressive HCC microenvironment through appropriately timed and optimally delivered combination viroimmunotherapies: advancing the use of oncolytic viruses to augment the killing of tumor cells for HCC, new Project 3 now will 1) test the clinical efficacy of a novel virotherapy combined with standard of care immunotherapy, 2) develop new combination viroimmunotherapies with increased potency in pre-clinical Sleeping Beauty models, and 3) develop a novel standard of care, virotherapy, CAR T-cell therapy combination. Collectively, this innovative, interactive, and highly collaborative translational research program is expected to advance prevention, early detection, diagnosis, treatment, and prognosis of patients with cancers of the liver and biliary tree.


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 = $2,286,710 )
2025	2025	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	001	5	3/10/2025	SUPPLEMENT FOR EXPANSION	$2,286,710
2025	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	002	6	3/10/2025	COMPETING CONTINUATION	$5,626
2025	2022	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	001	5	3/10/2025	SUPPLEMENT FOR EXPANSION	-$343
2025	2022	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	5	3/10/2025	NON-COMPETING CONTINUATION	-$5,282
														Subtotal = $2,286,710

Issue Date FY: 2024 ( Subtotal = $2,236,005 )
2024	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	001	6	8/28/2024	COMPETING CONTINUATION	$2,236,005
2024	2022	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	5	10/11/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,236,005

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	5	4/14/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $2,254,497 )
2022	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	002	5	9/14/2022	SUPPLEMENT FOR EXPANSION	$127,788
2022	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	001	5	9/12/2022	NON-COMPETING CONTINUATION	$2,070,878
2022	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	003	5	9/22/2022	NON-COMPETING CONTINUATION	$46,002
2022	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	004	5	9/23/2022	SUPPLEMENT FOR EXPANSION	$9,829
2022	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	4	6/6/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,254,497

Issue Date FY: 2021 ( Subtotal = $2,185,949 )
2021	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	003	4	8/16/2021	SUPPLEMENT FOR EXPANSION	$109,230
2021	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Research Manpower	004	4	9/17/2021	SUPPLEMENT FOR EXPANSION	$136,012
2021	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	002	4	8/12/2021	NON-COMPETING CONTINUATION	$1,940,707
2021	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	001	3	4/16/2021	NON-COMPETING CONTINUATION	$0
2021	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	3	12/16/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,185,949

Issue Date FY: 2020 ( Subtotal = $2,294,230 )
2020	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	003	3	9/1/2020	NON-COMPETING CONTINUATION	$2,294,230
2020	2019	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	2	4/23/2020	NON-COMPETING CONTINUATION	$0
2020	2019	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	002	2	8/31/2020	SUPPLEMENT FOR EXPANSION	$0
2020	2019	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	001	2	5/22/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,294,230

Issue Date FY: 2019 ( Subtotal = $2,357,460 )
2019	2019	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	002	2	9/10/2019	SUPPLEMENT FOR EXPANSION	$109,230
2019	2019	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	001	2	9/9/2019	SUPPLEMENT FOR EXPANSION	$109,230
2019	2019	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	2	8/30/2019	NON-COMPETING CONTINUATION	$2,139,000
														Subtotal = $2,357,460

Issue Date FY: 2018 ( Subtotal = $2,300,000 )
2018	2018	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	1	9/10/2018	NEW	$2,300,000
														Subtotal = $2,300,000

Grand Total All Awards = $15,914,851

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Mayo Clinic Hepatobiliary SPORE

Award Number: P50CA210964

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/10/2018

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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