A new type of therapy inspired by bacteria inside tumors offers a completely different approach to fighting cancer—not by attacking the cancer cells themselves head-on, but by precisely attacking the energy production systems they rely on to survive. A research team from the University of Illinois at Chicago borrowed strategies from bacteria in the tumor microenvironment to design an experimental anti-cancer drug that inhibits tumor growth by destroying the mitochondrial function of cancer cells.
In prostate cancer models, this treatment was particularly effective when used in combination with conventional radiation therapy, significantly curbing tumor growth. At the center of the study is a laboratory-synthesized peptide called aurB, derived from a bacterial protein that, upon entering cancer cells, attacks mitochondria, the cell's "powerhouses" responsible for producing energy. When the energy supply is cut off, it is difficult for tumor cells to continue to survive and expand. The relevant results have been published in the journal "Signal Transduction and Targeted Therapy".
Study leader Tohru Yamada, associate professor in the Department of Surgery and Biomedical Engineering at the University of Illinois at Chicago and a member of the University of Illinois Cancer Center, said that mitochondria are crucial to cell survival, and many cancer cells significantly change their number and activity in order to achieve rapid and invasive growth, so mitochondria themselves are an attractive therapeutic target. The scientific community has long known that bacteria exist in tumor tissues as part of the tumor microenvironment. In recent years, researchers have begun to systematically explore the anti-cancer molecular resources that these microorganisms may contain.
Previously, Yamada's team had discovered that a type of bacterial protein called cupredoxin has the ability to inhibit tumor growth. This type of protein contains copper and can transfer electrons between proteins. The team developed peptide drugs based on this protein and conducted extensive testing in adult clinical trials and children's brain cancer and other studies. However, this early candidate drug relies on the function of the tumor suppressor gene p53, which often has various mutations in different cancers and its functional status varies greatly, resulting in the drug being effective in some patients and having limited effect in others. To get rid of this limitation, the research team began to search for new anti-cancer factors that are "independent of p53 function."
To this end, the researchers turned to bacterial proteins that act directly on mitochondria, and eventually found another ceruloplasmin that acts through the mitochondrial pathway. In the latest study, the team analyzed tumor samples from breast cancer patients, sequenced the bacterial communities in them, and found that one bacteria stood out because it carried a type of ceruloplasmin called auracyanin, which was functionally similar to previously studied proteins. Based on this protein, scientists designed a new peptide drug aurB.
In laboratory cell experiments, aurB was able to enter the mitochondria of tumor cells and bind to a key enzyme, ATP synthase, thereby interfering with the production of ATP, the cell's main energy currency. The team tested aurB in cell lines lacking active p53 and in mouse models of prostate cancer that had lost response to hormone therapy. The results showed that when aurB was combined with standard prostate cancer therapy - radiation therapy - it significantly inhibited tumor growth without obvious signs of toxicity. Yamada pointed out that this combination regimen significantly enhanced the anti-tumor activity of the peptide, and a significant reduction in tumor volume was also observed in the classic tibial bone metastasis model. The pre-clinical data are encouraging.
Currently, the research team has patented aurB with support from the University of Illinois at Chicago's Office of Technology Management and is evaluating paths to advance this therapy into human clinical trials. Yamada also continues to dig deeper into bacterial resources to search for more candidate molecules that can be converted into anti-cancer drugs. He believes that auracyanin is just the tip of the iceberg of potential "drug treasure trove". "There are many other bacterial proteins that have the potential to be a source of anti-cancer drugs," he says. "We just haven't tried them all yet."