# Next Generation Rat Models of ER+ Breast Cancer

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $612,175

## Abstract

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.

## Key facts

- **NIH application ID:** 10464834
- **Project number:** 1R01CA271498-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Yi Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $612,175
- **Award type:** 1
- **Project period:** 2022-03-14 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464834

## Citation

> US National Institutes of Health, RePORTER application 10464834, Next Generation Rat Models of ER+ Breast Cancer (1R01CA271498-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10464834. Licensed CC0.

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