# Therapy for Metastatic breast cancer based on micro RNA silencing

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2021 · $580,298

## Abstract

Treatment options for patients with metastatic breast cancer are severely limited and ultimately rely on
palliative care representing an unmet clinical need. Previous studies have demonstrated that microRNAs play
a significant role in the formation of metastasis including those from breast cancer. Considering the paucity of
options for patients with metastasis from breast cancer, in this proposal we focused on targeting miR-10b
proven to be responsible for metastatic spread. While previous studies showed that miR-10b drives invasion
and migration of cancer cells from primary tumors, our recent discovery demonstrated that in metastatic cells it
is also responsible for cell viability and proliferation and that survival of metastatic cells crucially depends on
the high level of miR-10b expression. This discovery formed a cornerstone of our therapeutic strategy aimed at
specific eradication of metastatic tumor cells. This will be done using imaging-capable modular nanodrugs,
which distribute to lung, liver, bone, or brain metastases. These nanodrugs consist of magnetic nanoparticles
that carry locked-nucleic acid (LNA) oligonucleotides inhibiting microRNA-10b. Targeting moieties conjugated
to the nanoparticles facilitate their accumulation at distant metastatic sites. Previously we have demonstrated
the feasibility of the proposed approach. Delivery of the nanodrug to lymph nodes with already formed
metastases resulted in arrest of metastatic progression by inhibiting tumor cell proliferation and causing
apoptosis, which is a phenomenon that has not been described before. When treatment with the nanodrug was
combined with a low-dose of conventional chemotherapy (doxorubicin), there was regression and permanent
elimination of lymph node or lung metastases without relapse even after treatment was discontinued. Unlike
conventional chemotherapies, this therapeutic protocol was not associated with animal morbidity/mortality. In
the current application we propose to use the miR10b-inhibitory nanodrug in combination with low-dose
chemotherapy (where necessary) for targeting breast cancer metastases in distant organs. Noninvasive
imaging will be used to evaluate the delivery of the nanodrug. If successful, this approach could be a life-
extending (and possibly, life saving) alternative for patients with advanced metastatic disease for whom
salvage therapy is the only current option.

## Key facts

- **NIH application ID:** 10434241
- **Project number:** 7R01CA221771-04
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** ANNA MOORE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $580,298
- **Award type:** 7
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434241

## Citation

> US National Institutes of Health, RePORTER application 10434241, Therapy for Metastatic breast cancer based on micro RNA silencing (7R01CA221771-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10434241. Licensed CC0.

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