Starving Tumor Cells of Mitochondrial Fuel
Researchers at the University of Illinois Chicago (UIC) have developed an experimental cancer treatment, dubbed aurB, that targets the energy production of tumor cells. By utilizing a protein derived from bacteria found within the tumor microenvironment, the therapy disrupts mitochondrial function in preclinical prostate cancer models, effectively depriving cancer cells of their fuel supply.
Cancer cells often exhibit rapid, aggressive growth, requiring an altered and highly active mitochondrial state to meet their energy demands. According to findings published in the journal Signal Transduction and Targeted Therapy, the team identified a bacterial protein fragment, aurB, that interferes with this process.
Binding to the Cellular Powerhouse
The treatment works by entering the tumor cell’s mitochondria and binding to ATP synthase. This protein is essential for the production of adenosine triphosphate (ATP), the primary energy carrier in cells. By inhibiting ATP synthase, aurB prevents the tumor from generating the fuel necessary to sustain its rapid expansion. Tohru Yamada, senior author of the study and associate professor at UIC, noted that because cancer cells rely heavily on these “energy factories,” they represent a strategic target for therapeutic intervention.
Circumventing the p53 Mutation Barrier
Previous research into bacterial proteins, specifically cupredoxins, showed promise in suppressing tumor growth. However, those earlier treatments were often dependent on the p53 gene. Because p53 is frequently mutated in cancer patients—and these mutations vary significantly between individuals—the efficacy of p53-dependent treatments can be inconsistent.
The UIC team specifically sought a mechanism that functions independently of the p53 pathway. By analyzing breast cancer tumor samples and using DNA sequencing, the researchers identified a bacterial species containing a cupredoxin protein known as auracyanin. They subsequently engineered the aurB peptide to bypass the limitations of p53-reliant therapies.
Potent Results in Metastatic Models
In studies involving mouse models of hormone therapy-resistant prostate cancer, the combination of aurB and radiation therapy yielded significant results. The researchers observed a substantial reduction in tumor growth, with no evidence of significant toxicity.
“The combination significantly enhanced the activity of the peptide and the tumor became much smaller,” Yamada stated regarding the preclinical findings. The team successfully demonstrated this inhibitory effect using a tibial bone metastatic model.
Patenting a New Oncology Frontier
The University of Illinois Chicago has secured a patent for the aurB peptide through the university’s Office of Technology Management. While the research is currently in the preclinical stage, the team is exploring pathways to advance the therapy into human clinical trials.
Beyond aurB, researchers believe this discovery points to a broader opportunity in oncology. The tumor microenvironment is home to numerous unexplored bacterial proteins that may possess similar therapeutic potential. The study involved a multidisciplinary team from the UIC College of Medicine and the College of Engineering, including contributions from Drs. Martin Borhani, Aslam Ejaz, Ajay Rana, Enrico Benedetti, and Tapas K. Das Gupta.
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