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Gain-of-function mutant p53 and metabolic reprogramming in colorectal cancer

Award Number: R01CA260837
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Gain-of-function mutant p53 and metabolic reprogramming in colorectal cancer - Tumor suppressor p53 plays a central role in tumor prevention. p53 is frequently mutated in human cancer, including colorectal cancer (CRC). Many mutant p53 (mutp53) proteins not only lose tumor suppressive function of wild-type p53, but also gain new oncogenic activities to promote tumorigenesis, which is defined as mutp53 gain-of-function (GOF). Maintaining metabolic homeostasis is a novel and critical mechanism of p53 in tumor suppression. Cancer cells often display lipid metabolic reprogramming, which contributes greatly to cancer progression. Currently, the role and mechanism of mutp53 in cancer metabolic reprogramming are poorly defined. Our preliminary studies suggest that mutp53 drives lipid metabolic reprogramming as a critical GOF in CRC cells, and targeting lipid metabolic reprogramming compromises mutp53 GOF in colorectal tumorigenesis. Based on our preliminary results, we hypothesize that GOF mutp53 drives lipid metabolic reprogramming as a critical mechanism to promote colorectal tumorigenesis, which can be targeted for therapy in CRC carrying mutp53. In this proposed study, we will determine the role (Aim 1) and mechanism (Aim 2) of GOF mutp53 in driving lipid metabolic reprogramming in CRC. We will further assess targeting mutp53-driven lipid metabolic reprogramming as a potential therapeutic strategy for CRC carrying mutp53 (Aim 3). The goal of this study is to determine the mechanism of GOF mutp53 in CRC to provide effective targets and strategies for CRC therapy. Metabolic reprogramming and p53 mutations are common events in cancer, and have become extremely attractive targets for cancer therapy. We expect that the results from this proposed study will deepen our understanding of the role and mechanism of mutp53 in metabolic reprogramming and tumorigenesis, and provide the rationale and base for the development of new therapeutic targets and strategies for cancers carrying mutp53.


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 = $459,611 )
2025	2025	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Cancer Biology Research	000	5	3/6/2025	NON-COMPETING CONTINUATION	$413,649
2025	2025	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Cancer Biology Research	001	5	5/23/2025	NON-COMPETING CONTINUATION	$45,962
														Subtotal = $459,611

Issue Date FY: 2024 ( Subtotal = $436,631 )
2024	2024	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Cancer Biology Research	000	4	3/11/2024	NON-COMPETING CONTINUATION	$413,649
2024	2024	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Cancer Biology Research	003	4	4/16/2024	NON-COMPETING CONTINUATION	$22,982
2024	2023	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Cancer Biology Research	002	3	3/27/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$138,086
2024	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	195 LITTLE ALBANY ST	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Cancer Biology Research	001	2	3/27/2024	NON-COMPETING CONTINUATION	-$138,086
														Subtotal = $436,631

Issue Date FY: 2023 ( Subtotal = $450,420 )
2023	2023	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Cancer Biology Research	001	3	3/31/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$450,420
2023	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	195 LITTLE ALBANY ST	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Cancer Biology Research	000	2	3/31/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $450,420

Issue Date FY: 2022 ( Subtotal = $450,420 )
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	195 LITTLE ALBANY ST	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Cancer Biology Research	001	2	4/29/2022	NON-COMPETING CONTINUATION	$36,772
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	195 LITTLE ALBANY ST	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Cancer Biology Research	000	2	3/10/2022	NON-COMPETING CONTINUATION	$413,648
														Subtotal = $450,420

Issue Date FY: 2021 ( Subtotal = $440,108 )
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	195 LITTLE ALBANY ST	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Cancer Biology Research	000	1	3/25/2021	NEW	$440,108
														Subtotal = $440,108

Grand Total All Awards = $2,237,190

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Gain-of-function mutant p53 and metabolic reprogramming in colorectal cancer

Award Number: R01CA260837

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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