Researchers at the University of Illinois Chicago have engineered a novel cancer therapy derived from a bacterial protein naturally present within tumors, showing potent results when combined with radiation in early tests.
The experimental treatment, based on a fragment of bacterial protein called aurB, essentially starves cancer cells by disrupting their ability to produce energy. In preclinical prostate cancer studies, the approach halted tumor growth when paired with standard radiation therapy.
The discovery builds on a simple but powerful idea: tumors are not isolated masses but living ecosystems hosting communities of bacteria. Scientists have long known this, but only recently began asking whether those bacterial residents might supply compounds useful for fighting cancer.
Tohru Yamada, the study's senior author and an associate professor of surgery and biomedical engineering at UIC, explains the logic. "The mitochondria are very important for a cell to survive; they are the energy factories," Yamada said. "Many cancer cells exhibit altered mitochondrial number and activity, because a cancer cell has to grow aggressively and rapidly. Therefore, the mitochondria would be an ideal target for cancer therapy."
The research team identified aurB by studying tumor samples from breast cancer patients and using DNA sequencing to pinpoint bacteria living inside the tumors. One bacterial species stood out because it contained a protein called auracyanin with promising energy-blocking properties.
The researchers designed aurB as a synthetic peptide that enters tumor cell mitochondria and latches onto ATP synthase, a protein critical for generating ATP, the fuel cells need to function. By disrupting this mechanism, aurB cuts off the tumor's power supply.
When tested in cancer cell lines and mouse models of hormone therapy-resistant prostate cancer, aurB combined with radiation produced dramatic tumor shrinkage. "The combination significantly enhanced the activity of the peptide and the tumor became much smaller," Yamada said.
The approach overcomes a key limitation of earlier bacterial-based cancer treatments. Previous work by Yamada's lab identified a different bacterial protein that could suppress tumors, but its effectiveness depended on a gene called p53. Since p53 is frequently mutated in cancer patients with variations that differ person to person, that treatment works well for some but not others.
"We wanted to have an anti-cancer agent that doesn't use the p53 function," Yamada said. By targeting the mitochondria directly instead, aurB bypasses this problem entirely.
The University of Illinois Chicago has patented aurB and is exploring pathways to advance it into human clinical trials. Yamada emphasizes that auracyanin likely represents just the opening of a much larger opportunity. Countless bacterial proteins remain untested, and many could potentially yield entirely new cancer drugs.
"There are many other bacterial proteins that could be source of cancer drugs," Yamada said. "We simply haven't tried them yet."
The findings appear in the journal Signal Transduction and Targeted Therapy. The work involved collaborators from the UIC College of Medicine and UI Health, with the Department of Surgery providing essential support.
Author Jessica Williams: "Mining the tumor's own resident bacteria for weapons against it is exactly the kind of creative thinking oncology needs right now."
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