Tuesday, July 1, 2025 7/1/2025

Prostate Cancer Bone Metastasis Biology and Targeting

Award Number: P01CA098912
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2002
PERIOD OF PERFORMANCE END DATE: 02/28/2021

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Prostate Cancer Bone Metastasis Biology and Targeting - DESCRIPTION (provided by applicant): Lethal bone metastasis frequently develops in patients with castration-resistant prostate cancer (CRPC). Critically, the biology of this conditio remains uncertain. Our currently funded Program Project Grant (PPG) focuses on characterizing selected soluble factors, heparan sulfate proteoglycans (HSPG) and reactive oxygen species (ROS) secreted by cancer cells and cells in the tumor microenvironment, to develop biomarkers to predict PC progression and treatment response. Our progress during the current funding period includes several patents and the development of multiple antibodies recognizing HSPG fragments for potential commercialization as diagnostic/ prognostic biomarkers. We also humanized a therapeutic antibody against β2-microglobulin for clinical translation to treat PC bone metastasis. In this competitive renewal application, our long-term redefined goal is to pursue new concepts in the tumor microenvironment that redirect tumor cells toward a metastatic phenotype. These innovations include the discoveries that (1) metastasis can be coordinated by Metastasis Initiating Cells (MICs) (Project 1: Chung), (2) the HSPG perlecan and its degradative products are critical mediators of PC metastasis (Project 2: Farach-Carson); (3) cells with megakaryocyte and/or osteomimetic (MO-mimicry) properties reside in primary tumors and can be altered by stromal factors to metastasize to bone (Project 3: Bhowmick); and (4) epigenetic programming of the PC genome can affect cholesterol and sterol metabolism in a manner that promotes metastasis (Project 4: Freeman). To test these concepts, we will use approaches and resources unique to our team. We showed that MICs can reprogram non-metastatic dormant cells through a feed-forward action involving a RANK-mediated signaling network, provoking them to participate in bone colonization. This novel concept is supported by substantial data from animal models and a unique population of hormone-naïve PC patients with bone metastasis and pathologic specimens collected from patients with known overall survival. We will pursue the underlying biology of how circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) (Project 1- Chung), and endothelial and inflammatory cells (Project 2), are recruited to participate in the metastatic cascade. We propose to develop biomarkers to predict which patients will switch from indolent to aggressive disease. Our long range objectives will be achieved by identifying signaling pathways converging on critical nodes that can be targeted with drugs. Our team has developed a range of state-of-the-art methods and tools, including single cell methods of tumor cell isolation using NanoVelcro microfluidics, whole genome sequencing, quantitative IHC by multiplex quantum dot labeling (mQDL), ChIP-seq and RNA-seq analyses. We have demonstrated success in 3D culture of human DTCs, tissue recombinants comprised of engineered human and murine cells, and reliable models of human PC bone and soft tissue metastases.


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 = -$5,433 )
2025	2019	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	15	10/1/2024	SUPPLEMENT FOR EXPANSION	-$5,433
														Subtotal = -$5,433

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2019	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	15	12/13/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2019	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	001	15	4/29/2022	NON-COMPETING CONTINUATION	$0
2022	2019	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	15	10/15/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	15	4/29/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $1,683,090 )
2019	2019	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	15	2/21/2019	NON-COMPETING CONTINUATION	$1,587,650
2019	2019	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	001	15	2/27/2019	SUPPLEMENT FOR EXPANSION	$95,440
														Subtotal = $1,683,090

Issue Date FY: 2018 ( Subtotal = $1,668,059 )
2018	2018	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	003	14	5/22/2018	NON-COMPETING CONTINUATION	$163,690
2018	2018	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	002	14	4/27/2018	SUPPLEMENT FOR EXPANSION	$12,477
2018	2018	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	004	14	5/24/2018	SUPPLEMENT FOR EXPANSION	$1,868
2018	2018	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	14	3/1/2018	NON-COMPETING CONTINUATION	$1,473,214
2018	2018	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	001	14	3/20/2018	SUPPLEMENT FOR EXPANSION	$16,810
														Subtotal = $1,668,059

Issue Date FY: 2017 ( Subtotal = $1,883,158 )
2017	2017	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	001	13	2/23/2017	SUPPLEMENT FOR EXPANSION	$129,570
2017	2017	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	003	13	7/28/2017	SUPPLEMENT FOR EXPANSION	$116,372
2017	2017	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	002	13	6/7/2017	NON-COMPETING CONTINUATION	$185,520
2017	2017	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	13	2/22/2017	NON-COMPETING CONTINUATION	$1,451,696
														Subtotal = $1,883,158

Issue Date FY: 2016 ( Subtotal = $1,756,390 )
2016	2016	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	001	12	8/18/2016	SUPPLEMENT FOR EXPANSION	$110,892
2016	2016	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	12	5/3/2016	NON-COMPETING CONTINUATION	$1,645,498
														Subtotal = $1,756,390

Issue Date FY: 2015 ( Subtotal = $1,697,998 )
2015	2015	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	001	11	3/3/2015	COMPETING CONTINUATION	$1,697,998
2015	2013	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	10	3/3/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,697,998

Issue Date FY: 2013 ( Subtotal = $1,454,096 )
2013	2013	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	10	8/19/2013	NON-COMPETING CONTINUATION	$1,454,096
														Subtotal = $1,454,096

Issue Date FY: 2012 ( Subtotal = $1,549,929 )
2012	2012	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	9	8/9/2012	NON-COMPETING CONTINUATION	$1,549,929
														Subtotal = $1,549,929

Issue Date FY: 2011 ( Subtotal = $1,555,838 )
2011	2011	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	8	7/21/2011	NON-COMPETING CONTINUATION	$1,555,838
														Subtotal = $1,555,838

Issue Date FY: 2010 ( Subtotal = $1,606,847 )
2010	2010	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	001	7	7/14/2010	NON-COMPETING CONTINUATION	$1,606,847
2010	2009	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	6	11/3/2009	COMPETING CONTINUATION	$0
														Subtotal = $1,606,847

Issue Date FY: 2009 ( Subtotal = $1,651,359 )
2009	2009	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	6	9/22/2009	COMPETING CONTINUATION	$1,651,359
														Subtotal = $1,651,359

Issue Date FY: 2007 ( Subtotal = $1,513,950 )
2007	2007	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Cancer Biology Research	000	5	8/1/2007	NON-COMPETING CONTINUATION	$1,513,950
														Subtotal = $1,513,950

Issue Date FY: 2006 ( Subtotal = $1,512,918 )
2006	2006	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Cancer Biology Research	000	4	7/28/2006	NON-COMPETING CONTINUATION	$1,512,918
														Subtotal = $1,512,918

Issue Date FY: 2005 ( Subtotal = $1,508,950 )
2005	2005	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Cancer Biology Research	000	3	9/28/2005	NON-COMPETING CONTINUATION	$1,508,950
														Subtotal = $1,508,950

Issue Date FY: 2004 ( Subtotal = $1,469,563 )
2004	2004	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Cancer Biology Research	000	2	7/30/2004	NON-COMPETING CONTINUATION	$1,469,563
														Subtotal = $1,469,563

Issue Date FY: 2003 ( Subtotal = $1,524,683 )
2003	2003	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Cancer Biology Research	000	1	9/17/2003	NEW	$1,524,683
														Subtotal = $1,524,683

Grand Total All Awards = $24,031,395

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Prostate Cancer Bone Metastasis Biology and Targeting

Award Number: P01CA098912

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2002

PERIOD OF PERFORMANCE END DATE: 02/28/2021

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