UToledo Researcher Tackles Drug Resistance in Aggressive Breast Cancer

UToledo Researcher Tackles Drug Resistance in Aggressive Breast Cancer

A University of Toledo researcher has received a grant from the National Cancer Institute (NCI) of the National Institutes of Health (NIH) to investigate a new strategy for overcoming one of the most stubborn obstacles in treating triple-negative breast cancer: resistance to chemotherapy.

Dr. Yong (Kevin) Jiang, an associate professor in the Department of Cell and Cancer Biology and a member of UToledo's Northwest Ohio Cancer Research Institute, is leading the project, titled "Enhancing Chemotherapeutic Efficacy in Triple-Negative Breast Cancer via DSTYK Silence." This latest award of more than $374,000 brings total NIH funding for the project to more than $1.39 million across four years.

Triple-negative breast cancer (TNBC) is among the most aggressive forms of the disease, accounting for a disproportionate share of breast cancer deaths and offering patients fewer targeted treatment options than other subtypes. Chemotherapy remains the standard of care for TNBC, but many patients develop resistance to these drugs over time, sharply reducing their effectiveness.

Jiang's laboratory identified a protein called DSTYK - dual serine/threonine and tyrosine protein kinase - as a key driver of that resistance. His team found that TNBC cells that survive repeated exposure to chemotherapy produce significantly more of this protein than untreated cells. When DSTYK activity was blocked, chemotherapy-resistant cells became vulnerable to drug treatment again, dying in both laboratory and animal models.

"Our findings suggest that DSTYK plays a previously unknown and important role in allowing these cancer cells to survive chemotherapy," Jiang said. "By silencing this protein, we may be able to restore the effectiveness of existing drugs - without requiring entirely new therapies."

The research pursues a particularly novel delivery mechanism: engineered exosomes, tiny particles naturally released by cells, loaded with genetic material called siRNA designed to switch off DSTYK specifically in TNBC cells. In early preclinical models, these exosome-based particles promoted tumor regression and inhibited cancer spread.

The new funding will allow the team to further establish DSTYK as a prognostic biomarker in clinical TNBC cases and evaluate the approach in more advanced preclinical models.

The project has three main aims: uncovering the precise mechanism by which DSTYK promotes chemoresistance; determining whether DSTYK levels in tumors can predict patient outcomes; and testing the therapeutic potential of DSTYK-targeting exosomes in combination with chemotherapy.

Jiang joined UToledo faculty after originating this research at East Tennessee State University. His work in cancer cell biology focuses on the molecular underpinnings of tumor progression and resistance.

Breast cancer is the most common cancer among women in the United States, accounting for more than 15% of new cancer diagnoses and roughly 7% of all cancer-related deaths each year.

The Northwest Ohio Cancer Research Institute (NOCRI) is a collaborative, region-wide initiative dedicated to advancing cancer research, improving patient outcomes and strengthening the scientific and clinical community rooted in The University of Toledo's growing research enterprise. NOCRI brings together scientists, clinicians, engineers, data scientists, trainees and community partners to accelerate discovery and innovation.

The National Cancer Institute is the largest funder of cancer research in the world, supporting the infrastructure that sustains cancer research performed at NCI and at cancer centers, hospitals, community clinics and universities across the United States and around the world.