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Three dimensional nanoscale nuclear architecture mapping based taxonomy of precursor lesions for predicting colorectal cancer risk

Award Number: R01CA232593
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY The effectiveness of colorectal cancer (CRC) screening, with a concomitant increased emphasis on detection of even the smallest adenomas, has resulted in a new clinical challenge. An increased number of people are being identified as harboring an adenomatous polyp, the benign precursor to CRC. These patients are recommended to undergo surveillance, or repeated colonoscopy for monitoring for recurrence. The guidelines for surveillance intervals, based on polyp size and pathologic classification, do not accurately reflect individual’s risk for CRC progression. Due to the lack of reliable markers to stratify individual patient’s cancer risk after adenoma resection, surveillance colonoscopy is often improperly applied in clinical practice. Clinicians urgently need cost-effective tests that accurately distinguish high-risk patients in need of more frequent surveillance from low-risk patients for whom surveillance interval can be lengthened. Building on the imaging principle behind Spectral-Domain Optical Coherence Tomography (SD-OCT), we have developed a new approach for 3D nanoscale nuclear architecture mapping (3D-nanoNAM) on tissue biopsies routinely obtained for patients’ clinical care. We have shown that nanoNAM directly quantifies sub-microscopic alterations in the intrinsic 3D structural architecture of cell nuclei in unstained formalin-fixed, paraffin- embedded (FFPE) tissue sections with nanoscale sensitivity. The goal of this project is to develop a reliable risk taxonomy of nanoNAM markers that are associated with CRC progression, and rigorously validate their ability to consistently predict CRC progression risk in the context of colorectal adenoma. We will rigorously validate the carcinogenesis dependence of 3D nanoNAM markers in intestinal tumorigenesis using animal models and characterize their corresponding change during the acceleration and inhibition of tumorigenesis. We will also evaluate the use of nanoNAM markers to predict the recurrence risk of advanced adenomas. Success of this project will validate nanoNAM markers for CRC progression-risk and justify a future, larger- scale clinical study for employing nanoNAM as an objective, personalized stratification tool to guide establishment of the recommended time interval for surveillance colonoscopy.


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 = $0 )
2024	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Detection and Diagnosis Research	000	5	12/11/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $364,730 )
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Detection and Diagnosis Research	000	5	3/31/2023	NON-COMPETING CONTINUATION	$364,730
														Subtotal = $364,730

Issue Date FY: 2022 ( Subtotal = $414,155 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Detection and Diagnosis Research	001	4	5/11/2022	NON-COMPETING CONTINUATION	$33,809
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Detection and Diagnosis Research	000	4	3/11/2022	NON-COMPETING CONTINUATION	$380,346
														Subtotal = $414,155

Issue Date FY: 2021 ( Subtotal = $461,118 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Detection and Diagnosis Research	000	3	3/16/2021	NON-COMPETING CONTINUATION	$461,118
														Subtotal = $461,118

Issue Date FY: 2020 ( Subtotal = $437,317 )
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Cancer Detection and Diagnosis Research	000	2	4/17/2020	NON-COMPETING CONTINUATION	$437,317
														Subtotal = $437,317

Issue Date FY: 2019 ( Subtotal = $437,317 )
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Cancer Detection and Diagnosis Research	000	1	1/29/2019	NEW	$437,317
														Subtotal = $437,317

Grand Total All Awards = $2,114,637

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Three dimensional nanoscale nuclear architecture mapping based taxonomy of precursor lesions for predicting colorectal cancer risk

Award Number: R01CA232593

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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