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Modeling Bone Breast Tumor Cell Interactions to Predict and Prevent Metastasis

Award Number: R01CA304246
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/12/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

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Modeling Bone Breast Tumor Cell Interactions to Predict and Prevent Metastasis - Project Summary The overarching goal of this project is to establish a tunable in vitro 3D osteoconductive bone niche that permits reproducible analysis of key in vivo breast cancer cell-bone interactions and assessment of early interventions to prevent breast cancer bone metastasis. The bone niche will be developed with versatile, familiar biomaterials polyethylene terephthalate glycol (PETG), hydroxyapatite (HA), and collagen, using a novel process that allows inclusion of biologically relevant levels of mineral content. Our new engineered composite scaffolds are designed to investigate and model the conditions that optimally favor bone metastasis by breast cancer cells, specifically bone loss. We propose that the physicochemical features of our newly engineered 3D scaffolds can be tuned to mimic bone conditions and demonstrate clinically-relevant bone cell-cancer cell interactions through two aims. Aim 1 will define and validate functional biomimetic 3D scaffold bone tissue models, tunable from healthy to osteoporotic, while mimicking bone mineral density loss and remodeling and their effects on breast tumor growth. We will optimize the models to closely mimic cancer cell homing and cell-matrix interactions. We will benchmark against key features that define in vivo breast-bone metastases, including mineral turnover and tumor progression and will assess the key features of bone metastases in vivo and validate them in the bone-like environment. In vivo parameters assessed will include mineral turnover, tumor progression, and relevant surrogate markers and will be used to calibrate the in vitro models. Aim 2 will assess bone mineral density within the 3D bioengineered bone-like environment following therapeutic modulations of osteocyte and osteoclast activities and subsequent effects on tumor colonization and growth. We will assess the activities of osteocytes and osteoclasts in healthy and osteoporotic biomimetic 3D bone models and whether specific osteogenic drugs alter scaffolds. Effects of bone modulators in in vivo bone metastasis models will be compared and correlated to 3D bone system observations. The ability of tumor cell to colonize the 3D bone matrix will be assessed in conditions associated with normal and osteoporotic bone turnover. The relationship between the activity of osteoclasts/mineral deposition/scaffold pore size, and drug availability in dynamic engineered 3D bone will be determined. The potential of healthy and osteoporotic 3D engineered bone models to mimic, over time, the effects of bone modulators observed in vivo bone metastasis models will be tested. Mouse models provide the most appropriate approach to mimic the complexities of human cancer, bypassing the inherent variation observed in patients, and are essential to identify the critical set of parameters that will allow the calibration of robust 3D models. The completion of this project will (1) establish biomimetic healthy and osteoporotic 3D bone models with key tunable and reproducible features that support bone homeostasis, metastatic breast cancer cell homing, and proliferation in in vitro conditions; and (2) demonstrate the potential of appropriately mineralized 3D biomimetic models to predict and prevent bone metastasis.


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 = $479,860 )
2026	2026	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Cancer Biology Research	000	1	8/12/2026	NEW	$479,860
														Subtotal = $479,860

Grand Total All Awards = $479,860

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Modeling Bone Breast Tumor Cell Interactions to Predict and Prevent Metastasis

Award Number: R01CA304246

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/12/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

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