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Next Generation Rat Models of ER+ Breast Cancer

Award Number: R01CA271498
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/14/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Next Generation Rat Models of ER+ Breast Cancer - Title: Next Generation Rat Models of ER+ Breast Cancer Abstract: Despite the prevalence of estrogen receptor-positive (ER+) breast cancer (BCa), there are no mammalian models that are immunocompetent and metastasize spontaneously to clinically relevant organs such as bones. ER+ BCs comprise ~70% of BCa cases and are treated with surgical resection and adjuvant endocrine therapies. Although the 5-year survival rate is high, risk of metastatic recurrence persists for dec- ades, and 20-40% of ER+ BCa patients eventually succumb to metastatic disease, most often in bones. Our limited knowledge of ER+ BCa has been largely derived from oversimplified cell line models and in vitro experiments. Our available xenograft models exclude the critical immune component while genetically engineered mouse models (GEMMs) rarely stably maintain ER expression and rely on ER signaling – and none metastasize to bone, the most frequent site. As a result, very little is known about the initial tumori- genesis process and bone metastasis of ER+ BCa, which greatly impedes our effort to develop new prevention strategies or adjuvant therapeutics that can block/treat ER+ BCa bone metastasis. We have developed a series of rat ER+ BCa models by intraductal injection of viruses to introduce genetic alterations. Our preliminary data demonstrated that these rat ER+ mammary tumors: 1) developed in immunocompetent hosts, 2) showed endocrine therapy sensitivity or resistance, and 3) readily formed ER+ metastases including in bone – all of which are key properties that are lacking in existing BCa models. Based on these, we hypothesize that rat-based intraductal injection models (RIIMs) of breast cancer faithfully recapitulate human ER+ BCa in terms of tumor initiation, metastasis, and therapeutic responses. We will pursue the following three aims: (1) To characterize early progression of ER+ BCa in RIIM models. (2) To characterize the metastatic behaviors of ER+ BCa in RIIM models. (3) To credential ER+ RIIM models in recapitulating therapeutic responses and resistance mechanisms of human ER+ BCa.


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 = $595,831 )
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	4	5/22/2025	NON-COMPETING CONTINUATION	$59,584
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	4	3/3/2025	NON-COMPETING CONTINUATION	$536,247
														Subtotal = $595,831

Issue Date FY: 2024 ( Subtotal = $567,317 )
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	3	2/27/2024	NON-COMPETING CONTINUATION	$537,456
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	3	4/16/2024	NON-COMPETING CONTINUATION	$29,861
														Subtotal = $567,317

Issue Date FY: 2023 ( Subtotal = $759,830 )
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	2	2/16/2023	NON-COMPETING CONTINUATION	$585,230
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	2	7/24/2023	SUPPLEMENT FOR EXPANSION	$174,600
														Subtotal = $759,830

Issue Date FY: 2022 ( Subtotal = $612,175 )
2022	2022	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	1	3/14/2022	NEW	$612,175
														Subtotal = $612,175

Grand Total All Awards = $2,535,153

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Next Generation Rat Models of ER+ Breast Cancer

Award Number: R01CA271498

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/14/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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