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Therapeutic targeting Wnt5A signaling for advanced prostate cancer

Award Number: R01CA250082
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2020
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Therapeutic targeting Wnt5A signaling for advanced prostate cancer - Enzalutamide and abiraterone are initially effective for the treatment of castration-resistant prostate cancer (CRPC). However, resistance to both drugs occurs frequently through mechanisms which are incompletely understood. Evidence from both clinical and experimental studies demonstrate that Wnt signaling, particularly through Wnt5A, plays vital roles in promoting CRPC progression and induction of resistance to enzalutamide and abiraterone. Development of novel strategies targeting Wnt5A to overcome resistance is an urgent need. Preliminary and clinical data demonstrate that Wnt5A signaling is significantly activated in resistant CRPC cells and specimens from CRPC patients. Down regulation of Wnt5A inhibits AR/AR variants expression, suppresses cell growth, and resensitizes resistant cells to anti-androgen treatment. The objective of this proposal is to fully delineate the role of Wnt5A signaling in drug resistance and determine the efficacy of targeting Wnt5A using two novel strategies to overcome resistance. In Aim 1, we will determine the role of Wnt5A in the development of resistance to enzalutamide and abiraterone. In aim 2, we will evaluate the efficacy of two novel strategies targeting Wnt5A for inhibiting resistant CRPC tumor growth and re-sensitization to enzalutamide/abiraterone treatment. In aim 3, we will elucidate the mechanisms of action by Wnt5A inhibition in resistant CRPC. We hope that by completion of this study we will provide a novel therapeutic approach to treat advanced CRPC through targeting Wnt5A. We also expect that targeting Wnt5A in conjunction with enzalutamide/abiraterone therapy will increase the magnitude and duration of the benefits of second-generation antiandrogens.


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 = $367,236 )
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Treatment Research	001	5	6/9/2025	NON-COMPETING CONTINUATION	$36,724
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Treatment Research	000	5	11/26/2024	NON-COMPETING CONTINUATION	$330,512
														Subtotal = $367,236

Issue Date FY: 2024 ( Subtotal = $356,964 )
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Treatment Research	001	4	4/17/2024	NON-COMPETING CONTINUATION	$18,789
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Treatment Research	000	4	11/13/2023	NON-COMPETING CONTINUATION	$338,175
														Subtotal = $356,964

Issue Date FY: 2023 ( Subtotal = $374,008 )
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Treatment Research	001	3	3/15/2023	NON-COMPETING CONTINUATION	$30,533
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Treatment Research	000	3	11/9/2022	NON-COMPETING CONTINUATION	$343,475
														Subtotal = $374,008

Issue Date FY: 2022 ( Subtotal = $377,221 )
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Treatment Research	000	2	11/15/2021	NON-COMPETING CONTINUATION	$346,425
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Treatment Research	001	2	4/28/2022	NON-COMPETING CONTINUATION	$30,796
														Subtotal = $377,221

Issue Date FY: 2021 ( Subtotal = $397,216 )
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Treatment Research	000	1	12/1/2020	NEW	$397,216
														Subtotal = $397,216

Grand Total All Awards = $1,872,645

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Therapeutic targeting Wnt5A signaling for advanced prostate cancer

Award Number: R01CA250082

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2020

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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