# Enhancing chemotherapeutic efficacy in triple-negative breast cancer via DSTYK silence

> **NIH NIH R01** · EAST TENNESSEE STATE UNIVERSITY · 2024 · $326,143

## Abstract

Project Abstract
Breast cancer, the most prevalent cancer in women, is responsible for more than 15% of new
cancer cases and about 6.9% of all cancer-related death in the US. A major cause of therapeutic
failure in breast cancer is the development of resistance to chemotherapy, especially for triple-
negative breast cancer (TNBC), a type of breast cancer considered to be more aggressive and
have a poorer prognosis than other types of breast cancer. Therefore, how to overcome
chemoresistance is the major challenge to improve the life expectancy of TNBC patients.
Preliminary data demonstrate that TNBC cells surviving from the chronic treatment of
chemotherapeutic drugs show significantly higher expression of a special protein kinase, dual
serine/threonine and tyrosine protein kinase (DSTYK), than parental cells without treatment.
Additionally, from both in vitro and in vivo results, we found that both the knockout of DSTYK and
exosome-mediated DSTYK silence can lead to the apoptosis of chemoresistant cells upon drug
treatment. This novel finding suggests that DSTYK exerts a previously unknown and important
role in promoting chemoresistance. The objective of this proposal is to elucidate the novel role
and the underpinning mechanism of DSTYK in regulating chemoresistance in TNBC cells and
further explore the potential of exosome-mediated DSTYK silence in TNBC chemotherapy with
preclinical models. We hypothesize that DSTYK is a novel target for chemotherapy to induce
TNBC cell death. We will test our hypothesis with three specific aims. In Aim 1, we will investigate
the mechanism by which DSTYK promotes chemoresistance in TNBC cells. In Aim 2, we will
establish DSTYK as a prognostic biomarker in clinical TNBC. In Aim 3, we will evaluate the
therapeutic benefit of DSTYK-siRNA-exosomes in chemotherapy. We engineered exosomes
containing siRNA against DSTYK that can specifically target TNBC cells. We found these
engineered exosomes can significantly promote tumor regression and inhibit metastasis in both
cellular and orthotopic models treated with drugs. Successful completion of the proposed studies
will provide fundamental insights into the role of DSTYK in chemoresistance in TNBC cells and
will lay the essential foundation for the development of an exosome-mediated strategy targeting
DSTYK to significantly improve clinical TNBC chemotherapy.

## Key facts

- **NIH application ID:** 10824272
- **Project number:** 5R01CA272760-02
- **Recipient organization:** EAST TENNESSEE STATE UNIVERSITY
- **Principal Investigator:** Yong Jiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $326,143
- **Award type:** 5
- **Project period:** 2023-04-10 → 2025-01-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10824272

## Citation

> US National Institutes of Health, RePORTER application 10824272, Enhancing chemotherapeutic efficacy in triple-negative breast cancer via DSTYK silence (5R01CA272760-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10824272. Licensed CC0.

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