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Profiling chemical tumor microenvironment: Application for diagnostics & therapy

Award Number: R01CA192064
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2015
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Profiling chemical tumor microenvironment: Application for diagnostics & therapy - PROJECT SUMMARY/ABSTRACT A key role of the TME in cancer progression, treatment resistance, and as a target for therapeutic intervention is increasingly appreciated. Noninvasive in vivo EPR-based spectroscopy and imaging of tissue oxygenation (pO{2}), extracellular pH (pH{e}), redox, glutathione (GSH) and interstitial inorganic phosphate (Pi) provide unique insights into biological processes in the TME, and may serve as a tool for preclinical screening of anticancer drugs and optimizing TME-targeted therapeutic strategies. In this competitive renewal application, our new directions are built on knowledge and discoveries made during the previous funding period. There are two goals of our R01 renewal proposal. First is to further advance paramagnetic probes and magnetic resonance technology with a focus on improving probes biocompatibility, functionality, and developing multifunctional imaging modalities. Second is to utilize these advances and knowledge accumulated using spectroscopic modalities in the initial R01 project period to obtain further insights into the role of TME in cancer progression, and to test our hypothesis on the roles of interstitial inorganic phosphate in tumorigenesis. The specific aims are: (SA1) To advance molecular multifunctional EPR-based imaging technology and paramagnetic probes. The biocompatible derivatives of multifunctional trityl HOPE probe sensitive to acidity (pH{e}), oxygen (pO{2}) and phosphate (Pi) in Extracellular tissue microenvironment, and dual function nitroxide pH & redox probes will be optimized for concurrent multifunctional imaging using cutting edge imaging modalities, rapid scan EPR imaging and Overhauser-enhanced magnetic resonance imaging. (SA2) To perform molecular imaging of chemical TME as the mammary tumors progress to malignancy. Multifunctional spatially-resolved TME profiling will validate morphological and gene expression-based staging in a mouse model of breast cancer and will map tumor regions with different phenotypes. Tissue samples from the areas with the chemical TME characteristics of a malignant phenotype will be isolated and the TME study will be complemented with immunohistochemical, biochemical, and genetic tissue analysis, and with measurements of total phosphorus and phosphate (Pi) contents in blood. In summary, the developed multifunctional imaging techniques and probes will broaden the scope of preclinical EPR allowing for mapping of physiologically relevant tissue parameters in various disease models in cancers and beyond. New knowledge on stage-specific TME evolution during tumor progression is required to optimize TME-targeted anticancer therapies. It will also provide a scientific basis to evoke public awareness of high content of the phosphate-based modifiers in the processed food and the potential health risk.


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 = $327,013 )
2024	2024	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE ROAD	MORGANTOWN	WV	26505	MONONGALIA	USA	Cancer Detection and Diagnosis Research	000	11	6/28/2024	NON-COMPETING CONTINUATION	$327,013
														Subtotal = $327,013

Issue Date FY: 2023 ( Subtotal = $337,340 )
2023	2023	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE ROAD	MORGANTOWN	WV	26505	MONONGALIA	USA	Cancer Detection and Diagnosis Research	000	10	6/26/2023	NON-COMPETING CONTINUATION	$337,340
														Subtotal = $337,340

Issue Date FY: 2022 ( Subtotal = $337,339 )
2022	2022	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Cancer Detection and Diagnosis Research	000	9	7/25/2022	NON-COMPETING CONTINUATION	$337,339
														Subtotal = $337,339

Issue Date FY: 2021 ( Subtotal = $344,224 )
2021	2021	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Cancer Detection and Diagnosis Research	002	8	7/29/2021	NON-COMPETING CONTINUATION	$344,224
2021	2020	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Cancer Detection and Diagnosis Research	001	7	2/16/2021	COMPETING CONTINUATION	$6,980
2021	2019	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Cancer Detection and Diagnosis Research	000	6	2/16/2021	NON-COMPETING CONTINUATION	-$6,980
														Subtotal = $344,224

Issue Date FY: 2020 ( Subtotal = $344,224 )
2020	2020	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Cancer Detection and Diagnosis Research	000	7	3/11/2020	COMPETING CONTINUATION	$344,224
														Subtotal = $344,224

Issue Date FY: 2019 ( Subtotal = $332,830 )
2019	2019	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Cancer Detection and Diagnosis Research	000	6	7/25/2019	NON-COMPETING CONTINUATION	$332,830
														Subtotal = $332,830

Issue Date FY: 2018 ( Subtotal = $343,125 )
2018	2018	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Cancer Detection and Diagnosis Research	000	5	7/23/2018	NON-COMPETING CONTINUATION	$343,125
														Subtotal = $343,125

Issue Date FY: 2017 ( Subtotal = $343,125 )
2017	2017	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Cancer Detection and Diagnosis Research	000	4	7/19/2017	NON-COMPETING CONTINUATION	$343,125
														Subtotal = $343,125

Issue Date FY: 2016 ( Subtotal = $331,879 )
2016	2016	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	POB 6001, UNIV SVCS CTR #3038B	MORGANTOWN	WV	26506	MONONGALIA	USA	Cancer Detection and Diagnosis Research	002	3	7/19/2016	NON-COMPETING CONTINUATION	$331,879
2016	2015	OHIO STATE UNIVERSITY	1800 CANNON DR/700 LINCOLN TOW	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Detection and Diagnosis Research	000	1	3/23/2016	NEW	-$341,029
2016	2015	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	POB 6001, UNIV SVCS CTR #3038B	MORGANTOWN	WV	26506	MONONGALIA	USA	Cancer Detection and Diagnosis Research	001	2	3/24/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$341,029
														Subtotal = $331,879

Issue Date FY: 2015 ( Subtotal = $352,275 )
2015	2015	OHIO STATE UNIVERSITY	1800 CANNON DR/700 LINCOLN TOW	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Detection and Diagnosis Research	000	1	7/24/2015	NEW	$352,275
														Subtotal = $352,275

Grand Total All Awards = $3,393,374

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Profiling chemical tumor microenvironment: Application for diagnostics & therapy

Award Number: R01CA192064

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2015

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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