Monday, June 30, 2025 6/30/2025

Nutrient Regulation of Cancer Cell Growth

Award Number: R01CA215185
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/06/2017
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Nutrient Regulation of Cancer Cell Growth - SUMMARY Renal cell cancer (RCC) is the most common type of kidney cancer, and despite therapeutic advances, mortality remains high. While there are over a dozen RCC subtypes with different genomic drivers, metabolic reprogramming is a shared feature of tumorigenesis and progression across most of the major forms of kidney cancer and represents a targetable vulnerability in RCC. Our preliminary results show that RCCs and other cancers rely on the amino acid asparagine for tumor mTORC1 activity and growth, and methods to deplete tumor asparagine levels impair cancer cell proliferation and block cancer growth. Cancers acquire asparagine through two main routes: 1) consumption from the environment, and 2) biosynthesis from aspartate via asparagine synthetase (ASNS). Over the last 5 years, we found that simultaneous reduction of tumor asparagine consumption and biosynthesis blocks growth of lung, breast, and pancreas cancers in mice. Tumor asparagine consumption can be targeted using L-Asparaginase (ASNase), which hydrolyzes serum asparagine, or dietary asparagine restriction, which reduces serum asparagine levels. Tumor asparagine biosynthesis can be targeted using metformin, which through inhibiting complex I of the electron transport chain (ETC), reduces cancer cell production of aspartate, an obligate substrate for ASNS biosynthesis of asparagine. In this renewal proposal, we will investigate kidney cancer asparagine dependency to determine whether asparagine depletion can be broadly applied to treat patients with various subtypes of RCC. We will also determine the mechanism by which asparagine is sensed in cancer cells to impact mTORC1 activity and whether asparagine depletion impacts immune cell activation within the RCC tumor microenvironment.


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 = $649,928 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Biology Research	001	8	6/16/2025	NON-COMPETING CONTINUATION	$64,992
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Biology Research	000	8	1/7/2025	NON-COMPETING CONTINUATION	$584,936
														Subtotal = $649,928

Issue Date FY: 2024 ( Subtotal = $617,432 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Biology Research	001	7	1/16/2024	NON-COMPETING CONTINUATION	$584,936
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Biology Research	002	7	4/17/2024	NON-COMPETING CONTINUATION	$32,496
2024	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Biology Research	000	5	11/2/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $617,432

Issue Date FY: 2023 ( Subtotal = $663,928 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Biology Research	001	6	2/2/2023	COMPETING CONTINUATION	$663,928
2023	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Biology Research	000	5	1/27/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $663,928

Issue Date FY: 2022 ( Subtotal = $342,958 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Biology Research	001	5	5/5/2022	NON-COMPETING CONTINUATION	$27,997
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Biology Research	000	5	11/24/2021	NON-COMPETING CONTINUATION	$314,961
														Subtotal = $342,958

Issue Date FY: 2021 ( Subtotal = $350,158 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cancer Biology Research	000	4	11/18/2020	NON-COMPETING CONTINUATION	$332,649
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cancer Biology Research	001	4	1/21/2021	NON-COMPETING CONTINUATION	$17,509
														Subtotal = $350,158

Issue Date FY: 2020 ( Subtotal = $350,353 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cancer Biology Research	000	3	11/23/2019	NON-COMPETING CONTINUATION	$315,317
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cancer Biology Research	001	3	1/22/2020	NON-COMPETING CONTINUATION	$35,036
														Subtotal = $350,353

Issue Date FY: 2019 ( Subtotal = $340,025 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cancer Biology Research	000	2	11/16/2018	NON-COMPETING CONTINUATION	$340,025
														Subtotal = $340,025

Issue Date FY: 2018 ( Subtotal = $349,455 )
2018	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cancer Biology Research	000	1	12/6/2017	NEW	$349,455
														Subtotal = $349,455

Grand Total All Awards = $3,664,237

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Nutrient Regulation of Cancer Cell Growth

Award Number: R01CA215185

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/06/2017

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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