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Imaging and Genomic Signatures of Brain Tumor Heterogeneity and Evolution to Optimize Patient Management

Award Number: P01CA118816
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2007
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Imaging and Genomic Signatures of Brain Tumor Heterogeneity and Evolution to Optimize Patient Management - OVERALL: PROJECT ABSTRACT The overall goal of this renewal P01 proposal is to identify imaging and genomic signatures of brain tumor heterogeneity and evolution to optimize patient management of the two most common primary brain tumors in adults: glioblastoma and meningioma. The hallmark of glioblastoma is resistance to standard treatment with rapid progression at the time of recurrence. Although meningioma can be slow growing, a major proportion recur following standard surgery and radiation with a significant adverse impact on survival. A new, prognostically distinct, classification of meningioma based on DNA-methylation was recently developed. This renewal P01 will establish non-invasive imaging correlates of mechanistic genomic drivers of tumor evolution and intra-tumoral heterogeneity (Projects 1 and 2), to uniquely identify new therapeutic targets that can be rapidly evaluated by biologically relevant imaging metrics to assess early response to treatment (Projects 3 and 4). Building upon the demonstration of genomic heterogeneity in these lesions along with the recent technical advances in 1H and hyperpolarized 13C metabolic imaging that have facilitated the successful translation of [1- 13C] and [2-13C]-labeled pyruvate and enabled the development of a new imaging probe ([1-13C]alpha- ketoglutarate) we will: i) elucidate spatial and temporal imaging correlates of genomic underpinnings of intratumor heterogeneity and their functional impact in glioblastoma that confounds therapies (Project 1); ii) characterize meningioma evolution and heterogeneity by defining genomic mechanisms and therapeutic vulnerabilities that underlie imaging features of intratumor molecular heterogeneity (Project 2). 3-D imaging models of genomic data will be generated in both Projects 1 and 2 with additional synergistic interactions based approaches applied. Using 1H- and hyperpolarized 13C- MRS markers of NF2 loss and FOXM1 expression, Project 3 will identify metabolic imaging biomarkers in the preclinical setting that can stratify molecular groups of meningiomas. Project 4 will expand on Projects 1, 2 and 3 to develop and optimize novel 1H and 13C metabolic imaging methods in patients in order to monitor early response to targeted therapy in recurrent glioblastoma, and determine metabolic features of meningioma gene-expression groups, including with the development of a new [1-13C]alanine probe. The Administrative & Clinical Services, Biospecimen & Biomarker, and Imaging Tumor Heterogeneity & Metabolism Cores will be critical for directing and supporting all of the projects. Leveraging the expertise, unique infrastructure at UCSF, translational strengths of the investigators, and achievements to date from the current P01 and other NCI grants, the pioneering fundamental and translational cancer research described in this proposal will accelerate the implementation of innovative experimental genomic and metabolic imaging techniques. This rapid translation of non-invasive metabolic imaging and genomic signatures to assess brain tumor heterogeneity and evolution will provide new insights into potential therapeutic targets, enhance the evaluation of novel therapies, and assist in the optimal patient management.


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	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	002	16	3/14/2025	COMPETING CONTINUATION	$287
2025	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	15	3/14/2025	NON-COMPETING CONTINUATION	-$277
2025	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	001	15	3/14/2025	SUPPLEMENT FOR EXPANSION	-$10
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $2,654,906 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	002	16	9/13/2024	COMPETING CONTINUATION	$2,654,906
2024	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	001	15	9/6/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	15	9/5/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,654,906

Issue Date FY: 2023 ( Subtotal = $2,468,698 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	003	15	9/18/2023	NON-COMPETING CONTINUATION	$47,655
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	002	15	8/9/2023	SUPPLEMENT FOR EXPANSION	$85,963
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	001	15	8/2/2023	NON-COMPETING CONTINUATION	-$85,963
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	15	7/26/2023	NON-COMPETING CONTINUATION	$2,421,043
														Subtotal = $2,468,698

Issue Date FY: 2022 ( Subtotal = $2,364,762 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	14	7/26/2022	NON-COMPETING CONTINUATION	$2,278,799
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	001	14	7/27/2022	SUPPLEMENT FOR EXPANSION	$85,963
														Subtotal = $2,364,762

Issue Date FY: 2021 ( Subtotal = $2,365,321 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	003	13	9/21/2021	SUPPLEMENT FOR EXPANSION	$87,717
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	002	13	7/12/2021	NON-COMPETING CONTINUATION	$2,277,604
2021	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	001	12	10/15/2020	NON-COMPETING CONTINUATION	$0
2021	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	11	10/14/2020	COMPETING CONTINUATION	$0
														Subtotal = $2,365,321

Issue Date FY: 2020 ( Subtotal = $2,238,345 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	003	12	7/29/2020	NON-COMPETING CONTINUATION	$2,238,345
2020	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	001	11	1/21/2020	COMPETING CONTINUATION	$287
2020	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	002	11	5/22/2020	COMPETING CONTINUATION	$0
2020	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	10	1/21/2020	NON-COMPETING CONTINUATION	-$287
														Subtotal = $2,238,345

Issue Date FY: 2019 ( Subtotal = $2,157,708 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	11	9/18/2019	COMPETING CONTINUATION	$2,157,708
														Subtotal = $2,157,708

Issue Date FY: 2017 ( Subtotal = $2,175,899 )
2017	2017	UNIVERSITY OF CALIFORNIA, SAN FRANCISCO	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	002	10	7/24/2017	NON-COMPETING CONTINUATION	$2,175,899
2017	2016	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 420	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	001	9	12/29/2016	EXTENSION WITH OR WITHOUT FUNDS	$169,849
2017	2015	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 420	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	8	12/29/2016	NON-COMPETING CONTINUATION	-$169,849
														Subtotal = $2,175,899

Issue Date FY: 2016 ( Subtotal = $2,170,035 )
2016	2016	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	9	7/18/2016	EXTENSION WITH OR WITHOUT FUNDS	$2,170,035
														Subtotal = $2,170,035

Issue Date FY: 2015 ( Subtotal = $2,180,843 )
2015	2015	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	8	7/21/2015	NON-COMPETING CONTINUATION	$2,180,843
														Subtotal = $2,180,843

Issue Date FY: 2014 ( Subtotal = $2,101,713 )
2014	2014	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	7	8/14/2014	NON-COMPETING CONTINUATION	$2,101,713
														Subtotal = $2,101,713

Issue Date FY: 2013 ( Subtotal = $2,138,843 )
2013	2013	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	6	8/15/2013	COMPETING CONTINUATION	$2,138,843
														Subtotal = $2,138,843

Issue Date FY: 2011 ( Subtotal = $2,103,852 )
2011	2011	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Treatment Research	000	5	7/18/2011	NON-COMPETING CONTINUATION	$2,103,852
														Subtotal = $2,103,852

Issue Date FY: 2010 ( Subtotal = $2,185,508 )
2010	2010	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Treatment Research	000	4	7/15/2010	NON-COMPETING CONTINUATION	$2,185,508
														Subtotal = $2,185,508

Issue Date FY: 2009 ( Subtotal = $2,934,974 )
2009	2009	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Trans-NIH Recovery Act Research Support	001	3	9/2/2009	SUPPLEMENT FOR EXPANSION	$812,687
2009	2009	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Treatment Research	000	3	6/23/2009	NON-COMPETING CONTINUATION	$2,122,287
														Subtotal = $2,934,974

Issue Date FY: 2008 ( Subtotal = $2,188,358 )
2008	2008	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Treatment Research	000	2	7/28/2008	NON-COMPETING CONTINUATION	$2,188,358
														Subtotal = $2,188,358

Issue Date FY: 2007 ( Subtotal = $2,325,890 ) (Continued on the next page)
Grand Total All Awards = $36,755,655

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Imaging and Genomic Signatures of Brain Tumor Heterogeneity and Evolution to Optimize Patient Management

Award Number: P01CA118816

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2007

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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