A new scientific review challenges conventional approaches to treating aggressive cancers, suggesting that an unexpected biological factor may hold the key to improving treatment outcomes. Credit: Shutterstock

Scientists are exploring a potentially overlooked factor behind some of the most treatment-resistant cancers: bacteria lurking inside tumors.

Some of the most aggressive cancers may have an overlooked source of treatment resistance: bacteria living inside tumors. Researchers suggest that these microbes could interfere with chemotherapy, weaken immune defenses, and alter surrounding tissues. They propose that combining existing antibiotics with cancer drugs might help overcome resistance in certain difficult-to-treat cancers.

In a review published in Cancer Biology & Medicine, scientists from Nankai University, the University of Utah, and Tianjin Medical University Cancer Institute & Hospital argue that “all diagnosed PPO-tumors must be considered to be bacteria-infected.” Their proposal focuses on poor prognosis outcome (PPO) tumors, although the assumption that these tumors harbor bacterial infections remains unproven.

How Bacteria Could Help Tumors Resist Treatment

Pancreatic, colorectal, and certain biliary cancers can be especially difficult to treat. Their tumors often suppress immune responses, undergo rapid genetic changes, and develop dense fibrous barriers that restrict drug delivery.

Researchers have detected bacteria within several of these cancers, including Fusobacterium nucleatum, Escherichia coli, Enterococcus faecalis, and Pseudomonas species. Some microbes may promote inflammation, interfere with immune defenses, or chemically alter chemotherapy drugs, potentially reducing their effectiveness.

However, as the authors caution, “the mere presence of intratumoral bacteria does not always confer causation.” Cancer genetics and other features of the tumor environment can independently drive aggressive growth and treatment resistance.

Why Advanced Cancer Drugs Face Obstacles

Nanomedicine aims to improve chemotherapy by using microscopic carriers to deliver drugs directly into tumors. Although promising in animal studies, these technologies have often produced limited additional benefits in human patients.

One challenge involves the enhanced permeability and retention (EPR) effect, which can help nanoparticles accumulate in tumors through unusually permeable blood vessels. Human tumors are often more fibrous and structurally complex than experimental tumors, making drug penetration less predictable. The authors highlight an “overpromise” in translating results from rodent models into clinical treatments.

They also propose that bacterial infections might increase the permeability of tumor blood vessels, potentially improving drug delivery. However, this possibility has not been conclusively demonstrated in human cancers.

Could Antibiotics Restore Chemotherapy Effectiveness?

Rather than waiting for more advanced nanomedicines, the researchers propose combining conventional antibiotics and chemotherapy drugs without specialized carriers. The authors argue that “all diagnosed PPO-tumors must be treated from the onset with a carrier-free antibiotic/chemotherapeutic drug combination.”

Animal studies provide preliminary support for investigating this approach. In bacteria-infected tumor models, combining the antibiotic ciprofloxacin with the chemotherapy drug gemcitabine has helped restore treatment sensitivity and suppress tumor growth. Whether similar benefits occur in patients remains uncertain.

What Must Happen Before Clinical Use?

A major challenge is the lack of reliable clinical tests for detecting bacterial infections inside living tumors. Treating patients without confirming infection could also disrupt beneficial microbes and contribute to antibiotic resistance.

The researchers recommend examining existing patient records for evidence that antibiotic and chemotherapy combinations improve outcomes. They argue that “retrospective clinical verification can sometimes be the only pathway to clinical progress.”

Such research could help identify patients most likely to benefit, but additional clinical evidence is needed before routinely combining antibiotics with chemotherapy for aggressive cancers.

Reference: “Poor prognosis outcome tumors, bacteria-infected tumors and nanodrugs: current evidence and hypotheses towards a paradigm change for treatment” by Henk J. Busscher, David W. Grainger, JinPu Yu and Da-Yuan Wang, April 2026, Cancer Biology & Medicine.
DOI: 10.20892/j.issn.2095-3941.2025.0748

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