Wednesday, December 10, 2025 12/10/2025

Mechanical determinants of organ-selective metastatic colonization, dormancy and outgrowth

Award Number: U54CA261694
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/17/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Mechanical determinants of organ-selective metastatic colonization, dormancy and outgrowth - Overall: PROJECT SUMMARY Metastatic disease is responsible for the vast majority of cancer mortality. Understanding of the fundamental mechanisms leading to metastatic cancer has been hampered by the need for models that replicate the step- wise metastatic process in vivo, yet are amenable to tight control and facilitate high-resolution, time-lapse imaging and quantitative analysis of cell behavior. Over the past decade, our team has developed in vivo and in vitro methods capable of simulating many steps of the metastatic cascade including tumor cell invasion, intravasation, trapping in the microcirculation or adhesion to the vessel walls, and extravasation into the surrounding extracellular matrix. In parallel, we have developed computational studies that provided detailed insights often not possible through experiments. This collective prior work has shed new light on central aspects of single-cell and collective cell behavior during metastasis, and identified mechanical adaptations and vulnerabilities of the tumor cell with promise for targeted interventions. The goal of our proposed U54 Center is to employ these developed assays and methods in combination with new measurement techniques to interrogate the full spectrum of stressors experienced by tumor cells in the metastatic niche during arrest and extravasation, and couple these with parallel studies of changes in chromatin structure and the transcriptome of tumor cells (Core B). These changes are critical to mechano-adaptation of the tumor cells towards an organ-preferential initiation of a metastatic colony or transition to dormancy. A hallmark of our proposed center is the use of state- of-the-art in vitro (Project 1) and in vivo (Project 2) experiments and computation (Core A) to uncover and probe the factors that ultimately determine tumor cell fate. We anticipate that such integrated studies will provide new insights into metastatic cancer, not possible by the use of any method alone, and enhance our ability to identify and screen for new therapies to inhibit the tendency for metastatic spread of disease.


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 = $1,462,791 )
2025	2025	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Centers Support Grants	001	5	9/4/2025	NON-COMPETING CONTINUATION	$1,462,791
2025	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Centers Support Grants	000	4	4/23/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,462,791

Issue Date FY: 2024 ( Subtotal = $1,601,089 )
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Centers Support Grants	002	4	9/10/2024	SUPPLEMENT FOR EXPANSION	$95,400
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Centers Support Grants	001	4	9/4/2024	NON-COMPETING CONTINUATION	$1,505,689
2024	2023	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Centers Support Grants	000	3	5/28/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,601,089

Issue Date FY: 2023 ( Subtotal = $1,730,731 )
2023	2023	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Centers Support Grants	001	3	8/22/2023	NON-COMPETING CONTINUATION	$1,553,418
2023	2023	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Centers Support Grants	002	3	8/23/2023	SUPPLEMENT FOR EXPANSION	$177,313
2023	2022	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Centers Support Grants	000	2	3/14/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,730,731

Issue Date FY: 2022 ( Subtotal = $1,723,529 )
2022	2022	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Centers Support Grants	001	2	8/22/2022	NON-COMPETING CONTINUATION	$1,553,576
2022	2022	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Centers Support Grants	002	2	8/25/2022	NON-COMPETING CONTINUATION	$169,953
2022	2021	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Centers Support Grants	000	1	11/3/2021	NEW	$0
														Subtotal = $1,723,529

Issue Date FY: 2021 ( Subtotal = $1,542,971 )
2021	2021	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Centers Support Grants	000	1	9/17/2021	NEW	$1,542,971
														Subtotal = $1,542,971

Grand Total All Awards = $8,061,111

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Mechanical determinants of organ-selective metastatic colonization, dormancy and outgrowth

Award Number: U54CA261694

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/17/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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