Researchers at the University of Illinois at Chicago (UIC) have developed an experimental cancer treatment based on bacteria that naturally live within tumors.
Preclinical studies on prostate cancer have shown surprising results when this treatment is combined with radiation therapy. This approach stopped tumor growth by targeting the energy supply of cancer cells. The treatment is constructed from small pieces of a bacterial protein called aurB. According to the findings published in the magazine Signal transduction and targeted therapyaurB interfered with energy production within the mitochondria of tumor cells, effectively depriving them of the fuel needed for tumor growth.
“Mitochondria are very important for cell survival and are energy factories,” said Toru Yamada, lead author of the study, associate professor in UIC’s Department of Surgery and Biomedical Engineering, and member of the University of Illinois Cancer Center. “Because cancer cells need to proliferate aggressively and rapidly, many cancer cells have altered mitochondrial number and activity. Mitochondria would therefore be an ideal target for cancer therapy.”
Looking beyond the p53 gene
Scientists have long known that tumors have communities of bacteria that reside within what is known as the tumor microenvironment. More recently, researchers have begun investigating whether these bacteria may provide compounds that can be repurposed to treat cancer.
Previous research by Yamada’s lab identified bacterial proteins known as cupredoxins that may inhibit tumor growth. Cupredoxins are copper-containing proteins that help transfer electrons between other proteins.
Based on this discovery, the team developed a peptide drug and tested it extensively, including clinical trials in adults and a study of brain tumors in children.
However, the effectiveness of that peptide depends on a gene called p53. p53 is frequently mutated in cancer patients, and these mutations vary from person to person, so treatments may work for some patients and not for others.
“We aimed for an anticancer drug that does not utilize the function of p53,” says Professor Yamada.
Targeting cancer’s energy factories
To find a different approach, the researchers looked for bacterial proteins that act through mitochondria rather than the p53 pathway. Their search led to the discovery of another cupredoxin protein.
For the new study, the team analyzed tumor samples taken from breast cancer patients and used DNA sequencing to identify the bacteria present within the tumors. One bacterial species received particular attention because it contained a cupredoxin protein known as auracyanin, which had a similar function to previously studied proteins.
The researchers then designed a peptide based on auracyanin and named it aurB. Laboratory experiments revealed that aurB enters the mitochondria of tumor cells and binds to ATP synthase, a protein that plays a key role in producing ATP, the main energy source used by cells.
Excellent results in prostate cancer models
The research team evaluated aurB in cancer cell lines lacking activated p53 and in mouse models of hormone therapy-resistant prostate cancer.
When combined with radiotherapy, one of the standard treatments for prostate cancer, aurB significantly reduced tumor growth without any signs of significant toxicity.
“This combination significantly enhanced the activity of the peptide and made the tumors much smaller,” Yamada said. “This approach is promising. We demonstrated significant inhibition of tumor growth preclinically using a well-established tibial metastasis model.”
Search for tumor bacteria as future cancer treatment drugs
UIC patented aurB with support from the university’s Technology Management Office. Researchers are currently exploring opportunities to advance this therapy into human clinical trials.
At the same time, Yamada believes auracyanin may be just the beginning of a bigger opportunity. Countless bacterial proteins remain unexplored, many of which could form the basis of future cancer treatments.
“There are many other bacterial proteins that have the potential to be raw materials for anti-cancer drugs,” Yamada says. “We just haven’t tried it yet.”
Dr. Yamada worked with collaborators at the School of Medicine and UI Health and credited the Department of Surgery, including the physicians. The contributions of Martin Borhani, Aslam Ejaz, Ajay Rana, Enrico Benedetti, and Tapas K. Das Gupta played an important role in the success of the project.
Other UIC authors of the study include Dr. Samer A. Naffouje, Dr. Duy Binh Tran, Dr. Konstantin Christov, Dr. Albert Green, Dr. Ngoc Hai Trieu Phong, Dr. Tapas K. Das Gupta from the School of Medicine, and Dr. Weiguo Li from the School of Engineering.
