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Modeling bone metastasis and tumor dormancy in prostate cancer

Award Number: U01CA313321
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/24/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2031

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Modeling bone metastasis and tumor dormancy in prostate cancer - Project Summary/Abstract Our research aims to uncover mechanisms that promote bone metastasis, which is the major cause of cell death for prostate cancer. We have generated a series of genetically-engineered mouse models (GEMMs) that enable investigations of the de novo evolution of prostate cancer metastasis as it arises in the whole organism in the context of the native microenvironment. These GEMMs recapitulate key gene/pathway alterations that are altered in human metastatic prostate cancer, and they incorporate lineage-tracing that allows for visualization, isolation, and molecular characterization of tumor cells and their descendant metastatic cells. To study bone tropism, we will investigate a series of GEMMs that display a range of prostate cancer phenotypes, from non-metastatic to highly metastatic, including bone metastasis. Tumors from GEMMs that develop bone metastases display strong transcriptomic differences, including enrichment of epithelial- mesenchymal transition (EMT) and expression of nuclear matrix proteins (TMPO(Lap2)). To study tumor dormancy, we will investigate a GEMM that displays features of tumor dormancy, including dissemination and seeding to bone without formation of overt metastases. Transcriptomic differences in tumors from GEMMs that develop bone metastases versus those in the dormancy model include a shift in metabolism from oxidative phosphorylation to glycolysis. In addition, major extrinsic differences that distinguish the highly metastatic versus the non-metastatic and dormancy models include profound differences in immune cell populations, most notably in neutrophils. Thus, we will investigate the hypothesis that the acquisition of bone metastasis requires adaptive intrinsic changes in the tumor cells, including EMT and alterations in the nuclear matrix, as well as extrinsic changes in the accumulation and distribution of immune populations, while the transition from dormancy to overt metastasis may require additional adaptations such as in metabolic functions. In Aim 1, we will identify cell- intrinsic mechanisms responsible for bone tropism and study how they may be altered in tumor dormancy. In Aim 2, we will investigate extrinsic differences in the tumor immune compartment in metastatic versus non- metastatic tumors and bone, and investigate how these immune cell populations contribute to metastasis and may be affected in tumor dormancy. In Aim 3, we will capitalize on our ability to track, isolate, and study all stages of metastasis in our GEMMs to study metastatic clonal dynamics using an in vivo evolving barcode lineage-tracing system to fully characterize cell states and their evolution over time. Relevance for MetNet: We will undertake a whole-body, systems-level approach to deciphering the dynamic mechanisms of metastasis in vivo using clinically-validated experimental models. Our team is highly collaborative and uniquely qualified to implement novel technological advances for identifying and tracking tumor, metastatic, and circulating tumor cells in vivo.


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: 2026 ( Subtotal = $681,310 )
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Biology Research	001	1	6/30/2026	NEW	-$139,545
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Biology Research	000	1	6/26/2026	NEW	$820,855
														Subtotal = $681,310

Grand Total All Awards = $681,310

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Modeling bone metastasis and tumor dormancy in prostate cancer

Award Number: U01CA313321

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 06/24/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2031

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