Thursday, July 3, 2025 7/3/2025

Influence of bone microenvironment on drug resistance in prostate cancer bone metastasis

Award Number: R01CA230744
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/19/2019
PERIOD OF PERFORMANCE END DATE: 12/31/2025

Group Awards By:

View Award Description

Influence of bone microenvironment on drug resistance in prostate cancer bone metastasis - In the United States, over 80% of prostate cancer patients die with bone metastases. Second line hormonal therapies such as enzalutamide only improve overall patient survival by a few months in about 50% of the patients, and almost all patients develop drug resistance. Thus, there is an urgent need to determine the mechanisms of drug resistance and to develop new approaches for overcoming such resistance and for better treatment of prostate cancer bone metastasis. Enzalutamide is a small-molecule inhibitor of the androgen receptor (AR). Our preliminary study demonstrated that although enzalutamide inhibited the tumor growth of castration-resistant prostate cancer C4-2B cells when xenografted orthotopically or subcutaneously, it had no effect on the growth of C4-2B tumors in the bone and the development of bone lesions. This data highlights a crucial role of the microenvironment in enzalutamide resistance in prostate cancer bone metastasis. Interestingly, we found that enzalutamide significantly and specifically reduced the TGF-β type II receptor (TGFBR2) protein in osteoblasts. This observation was also confirmed in prostate cancer patients who had undergone the second line hormonal therapies such as enzalutamide. To determine the role of TGFBR2 in the osteoblasts during bone metastasis, we used a mouse model (Tgfbr2Col1CreERT KO) with inducible Tgfbr2 knockout specifically in the osteoblasts. We found that Tgfbr2 KO in osteoblasts significantly promoted prostate cancer bone metastasis. Based on these results, we hypothesize that reduction of TGFBR2 in osteoblasts caused by enzalutamide results in resistance to the drug in prostate cancer bone metastasis. The objectives of this proposal are to determine how enzalutamide decreases osteoblast TGFBR2 and thus promotes prostate cancer bone metastasis and to identify novel approaches to counteracting the enzalutamide resistance.


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 = $0 )
2025	2024	UNIVERSITY OF TOLEDO	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	000	6	1/9/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $335,749 )
2024	2024	UNIVERSITY OF TOLEDO	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	001	6	4/15/2024	NON-COMPETING CONTINUATION	$17,672
2024	2024	UNIVERSITY OF TOLEDO	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	000	6	1/11/2024	NON-COMPETING CONTINUATION	$318,077
														Subtotal = $335,749

Issue Date FY: 2023 ( Subtotal = $346,350 )
2023	2023	UNIVERSITY OF TOLEDO, THE	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	000	5	12/23/2022	NON-COMPETING CONTINUATION	$318,077
2023	2023	UNIVERSITY OF TOLEDO, THE	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	001	5	3/17/2023	NON-COMPETING CONTINUATION	$28,273
														Subtotal = $346,350

Issue Date FY: 2022 ( Subtotal = $346,350 )
2022	2022	UNIVERSITY OF TOLEDO, THE	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	001	4	2/1/2022	NON-COMPETING CONTINUATION	$0
2022	2022	UNIVERSITY OF TOLEDO, THE	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	004	4	4/28/2022	NON-COMPETING CONTINUATION	$28,273
2022	2022	UNIVERSITY OF TOLEDO, THE	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	000	4	1/25/2022	NON-COMPETING CONTINUATION	$318,077
2022	2022	UNIVERSITY OF TOLEDO, THE	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	002	4	3/14/2022	NON-COMPETING CONTINUATION	$0
2022	2020	UNIVERSITY OF TOLEDO, THE	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	003	3	3/23/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $346,350

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	VAN ANDEL RESEARCH INSTITUTE	333 BOSTWICK AVE NE	GRAND RAPIDS	MI	49503	KENT	USA	Cancer Biology Research	001	2	2/2/2021	NON-COMPETING CONTINUATION	-$81,206
2021	2020	UNIVERSITY OF TOLEDO, THE	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	003	3	5/17/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2021	2020	UNIVERSITY OF TOLEDO, THE	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	002	3	2/2/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$125,663
2021	2019	VAN ANDEL RESEARCH INSTITUTE	333 BOSTWICK AVE NE	GRAND RAPIDS	MI	49503	KENT	USA	Cancer Biology Research	000	1	2/2/2021	NEW	-$44,457
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $484,625 )
2020	2020	UNIVERSITY OF TOLEDO, THE	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	003	3	8/31/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$50,000
2020	2020	VAN ANDEL RESEARCH INSTITUTE	333 BOSTWICK AVE NE	GRAND RAPIDS	MI	49503	KENT	USA	Cancer Biology Research	001	2	8/19/2020	NON-COMPETING CONTINUATION	-$353,419
2020	2020	UNIVERSITY OF TOLEDO, THE	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	002	3	8/19/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$353,419
2020	2020	VAN ANDEL RESEARCH INSTITUTE	333 BOSTWICK AVE NE	GRAND RAPIDS	MI	49503	KENT	USA	Cancer Biology Research	000	2	3/2/2020	NON-COMPETING CONTINUATION	$434,625
														Subtotal = $484,625

Issue Date FY: 2019 ( Subtotal = $434,625 )
2019	2019	VAN ANDEL RESEARCH INSTITUTE	333 BOSTWICK AVE NE	GRAND RAPIDS	MI	49503	KENT	USA	Cancer Biology Research	000	1	4/19/2019	NEW	$434,625
														Subtotal = $434,625

Grand Total All Awards = $1,947,699

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Influence of bone microenvironment on drug resistance in prostate cancer bone metastasis

Award Number: R01CA230744

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/19/2019

PERIOD OF PERFORMANCE END DATE: 12/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer