# Modulation of Epigenetic Target in the Bone to Treat Breast Cancer Metastasis

> **NIH NIH R01** · RICE UNIVERSITY · 2024 · $619,441

## Abstract

PROJECT SUMMARY/ABSTRACT
In the clinic, primary breast tumors are usually surgically removed soon after diagnosis, often leaving patients
“tumor-free”. However, 20-40% of breast cancer survivors will eventually suffer metastasis to distant organs,
sometimes years after surgeries. Bone metastasis is the most frequently occurring metastasis of breast cancer.
Our long-term goals are to elucidate the biology underlying the survival and progression of bone metastases,
which will inform the design of therapeutic strategies against these latent tumor cells, through a fruitful
collaboration between labs at Rice University and Baylor College of Medicine. The overall goal of this proposal
is to develop bone tumor-targeting epigenetic inhibitors and demonstrate their efficacy against bone
micrometastases as well as further multi-organ metastases seeding from bone lesions. Our preliminary data
establish that: (1) epigenetic inhibitors modified with bisphosphonates, have superb binding affinity for bone, and
exhibit enhanced bone metastasis sites targeting in vivo; and (2) epigenetic inhibitors modified with
bisphosphonates exhibited improved activities for inhibiting metastatic seeding from bone lesions to other
organs; and (3) an intra-iliac artery (IIA) injection, developed in our lab, can be used to effectively model the
bone metastatic niche, providing a powerful platform for evaluating the therapeutic efficacy against bone
metastatic cancers and “metastasis-to-metastasis” seeding from bone lesions. Based on these results, the first
research direction will focus on engineering current epigenetic inhibitors for breast cancer therapy with bone-
homing moiety. Next, we will study their effects on the survival and progression of breast cancer bone metastases
using both syngeneic and xenograft nude mouse models. Furthermore, we will dissect the molecular
mechanisms underlying the benefits of bone tumor-targeting epigenetic inhibitors. An enhanced therapeutic
profile for these bone-specific epigenetic inhibitors on breast cancer will inform the extension of these treatments
to other bone cancers and diseases.

## Key facts

- **NIH application ID:** 10880591
- **Project number:** 5R01CA277838-02
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Han Xiao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $619,441
- **Award type:** 5
- **Project period:** 2023-07-03 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880591

## Citation

> US National Institutes of Health, RePORTER application 10880591, Modulation of Epigenetic Target in the Bone to Treat Breast Cancer Metastasis (5R01CA277838-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10880591. Licensed CC0.

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