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Interrogating Type I Interferon signaling in breast cancer brain metastasis

Award Number: R01CA279117
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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Interrogating Type I Interferon signaling in breast cancer brain metastasis - PROJECT SUMMARY The brain is one of the common organs for breast cancer recurrence. Breast cancer brain metastasis is increasingly becoming a significant clinical problem due to its rising incidence and limited efficacy of existing systemic therapies. Metastasis is the consequence of favorable interactions between the invaded cancer cells and the microenvironment in the distal organ. To cancer cells, the brain has the most unique microenvironment since the stromal cells in the brain do not exist in any other organs. This explains why therapeutic strategies, which efficiently diminish primary and non-brain metastatic breast tumors, are ineffective in controlling the established brain lesions. Our current work aims to understand the unique brain metastasis microenvironment and delineate how it facilitates metastatic outgrowth. Type I interferon (IFN) signaling is a well-recognized anti-tumor pathway. However, experiments from our animal models show that type I response in astrocytes, the unique brain stromal cells, has a pro-metastatic effect in the brain. Based on these findings, we will further address the following questions: 1) Define the underlying mechanisms in how the type I IFN response in astrocytes mediates brain metastasis. We will test the hypothesis that the activated IFN response in astrocytes helps the recruitment of specific immune cells into the brain lesions. 2) Validate the type I IFN activation at different stages of brain metastasis. We will apply the top-notch imaging technique in our mouse models to directly visualize cellular and molecular changes as they occur in real-time, and validate these observations in clinical samples. 3) Investigate the therapeutic effect of inhibition of immune cell recruitment on brain metastasis. We will not only identify the druggable targets, but also optimize the therapeutic windows in our pre-clinical mouse models. Overall, our idea is that once we know how the brain microenvironment helps cancer growth in the brain, we can focus our efforts on stopping it. Our research proposal will yield real and actionable targets on brain microenvironment, instead of on cancer cells, to treat brain metastasis. More importantly, our studies on tracking the dynamic changes during brain metastatic process will help identify the optimal therapeutic strategies to effectively treat brain metastasis and minimize potential side effect.


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 = $546,142 )
2026	2026	THE INSTITUTE FOR CANCER RESEARCH	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Cancer Biology Research	000	3	4/29/2026	NON-COMPETING CONTINUATION	$546,142
														Subtotal = $546,142

Issue Date FY: 2025 ( Subtotal = $546,142 )
2025	2025	THE INSTITUTE FOR CANCER RESEARCH	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Cancer Biology Research	001	2	9/12/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$546,142
2025	2024	THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	000	1	9/11/2025	NEW	$0
2025	2024	THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	002	1	9/26/2025	NEW	$0
														Subtotal = $546,142

Issue Date FY: 2024 ( Subtotal = $529,002 )
2024	2024	THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	000	1	12/1/2023	NEW	$529,002
														Subtotal = $529,002

Grand Total All Awards = $1,621,286

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Interrogating Type I Interferon signaling in breast cancer brain metastasis

Award Number: R01CA279117

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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