A team of scientists at Purdue University has uncovered a potential new therapeutic target for triple-negative breast cancer, a particularly aggressive form of the disease that currently lacks targeted treatment options.
The research, led by Kyle Cottrell, an assistant professor of biochemistry, and biochemistry graduate student Addison Young, focuses on double-stranded ribonucleic acid (dsRNA)-binding proteins. Their findings were highlighted on Purdue’s College of Agriculture website.
“Triple-negative breast cancer is a particularly deadly form of breast cancer that currently lacks targeted therapies,” Cottrell said.
While most people are familiar with RNA as a single-stranded molecule, the team emphasized that double-stranded RNAs exist and are recognized by specialized proteins in cells. These proteins, known as dsRNA sensors, activate pathways to fight viral infections. However, problems arise when these pathways are activated in the absence of infection, which can lead to inflammation.
“This process has to be carefully regulated,” Cottrell explained. “As we age, cells lose the ability to control these pathways, leading to unintended activation and chronic inflammation.”
The research also explores the concept of viral mimicry, a cellular state that can enhance the effectiveness of certain cancer immunotherapies. Viral mimicry allows cells to appear as if they are infected with a virus, triggering defensive pathways that can help combat tumors.
Cottrell’s team specifically studied the protein PACT, a dsRNA-binding protein, and its interaction with RNA-activated protein kinase (PKR). Previous research had shown conflicting roles for PACT, but the Purdue team demonstrated that PACT acts as a suppressor of PKR in triple-negative breast cancer cells. PKR is a universal cellular sensor that detects viral dsRNAs and initiates protective responses.
By identifying PACT and other related proteins as key regulators, the team highlighted their potential as therapeutic targets. “Triple-negative breast cancer appears particularly sensitive to PACT depletion, making it a promising candidate for targeted therapy,” Cottrell said.
Current chemotherapy treatments for triple-negative breast cancer affect all dividing cells, causing significant side effects. Targeting PACT could provide a more precise approach, sparing healthy cells while attacking cancerous ones.
The researchers also noted the importance of dimerization—the fusion of two protein molecules—in regulating PACT function. Unlike typical enzyme targets, PACT’s activity cannot be inhibited by conventional methods. Instead, the team is exploring ways to disrupt its dimerization, potentially blocking its function and providing a novel therapeutic avenue.
This research is part of Purdue’s One Health initiative, which integrates studies across human, animal, and plant health. The project received support from the Ralph W. and Grace M. Showalter Research Trust Award, the National Institutes of Health, the Purdue Institute for Cancer Research, and the Department of Biochemistry in Purdue’s College of Agriculture.
