‘Bugs Delivering Drugs’: Novel Approach to Colorectal Cancer Treatment
Researchers at Baylor University have pioneered a new strategy in the fight against colorectal cancer, utilizing modified bacteria to deliver cancer-killing proteins directly into tumor cells. The findings, published in Cell Chemical Biology, offer a promising avenue for more effective and targeted cancer therapies.
The Challenge of Colorectal Cancer
Colorectal cancer remains a significant health concern, accounting for the second-most cancer-related deaths in 2025, according to the National Cancer Institute 1. This underscores the urgent need for innovative treatment strategies.
Harnessing Bacteria for Drug Delivery
Building on the growing field of bacterial cancer therapies, the research team, led by Dr. Michael S. VanNieuwenhze, attached saporin – a potent cancer-killing toxin – to the surface of Listeria monocytogenes. Listeria, commonly known as a food-borne bacterium, possesses the unique ability to penetrate human cells, making it a potentially valuable therapeutic agent 1.
“Our team asked the question, ‘What if we could hook saporin on the surface of a bug and let the bug get delivered into the cell as it normally would?’ We could then take advantage of chemistry inside the cell to release saporin to kill the cancer cell. That, in a nutshell, is what we were doing, and we were able to get it to work,” explained Dr. VanNieuwenhze 1.
How it Works: Listeria as a Cytotoxin Delivery Vehicle
The study details two approaches to Listeria monocytogenes-mediated cytotoxin delivery: endolysosome targeting using SN38/Dox-ADCs and cytoplasm targeting using saporin 2, 3. Researchers demonstrated that delivering saporin via Listeria significantly enhanced cytotoxicity compared to traditional antibody-drug conjugates (ADCs) 2.
Wyatt Paulishak, a Baylor doctoral student involved in the research, highlighted the bacterium’s unique properties: “What makes it so useful from a therapeutic perspective is that it is an intracellular bug, which gives it unique access to the compartments inside cells. As a living bug we can modify it to make it safer and more effective. It further has a significant immunotherapy component to it and is naturally anti-cancer, and we look at it as a drug-delivery vehicle.” 1
Increased Toxicity and Future Directions
The research team chemically attached saporin to the bacteria and observed a multiplied ability to fight cancer. Saporin is only toxic once inside a cell, and Listeria effectively facilitates this delivery 1. In vitro and in vivo testing in mice demonstrated a significant increase in toxicity with this approach 1.
Dr. VanNieuwenhze envisions future research focusing on genetic strategies to enhance safety and scalability, with the ultimate goal of developing a therapeutic that could potentially be administered orally 1.
Key Takeaways
- Researchers are exploring the employ of modified Listeria monocytogenes bacteria to deliver cancer-killing toxins directly into tumor cells.
- This approach has shown promising results in preclinical studies, demonstrating increased cytotoxicity compared to traditional methods.
- The unique ability of Listeria to penetrate cells makes it a valuable tool for targeted drug delivery.
- Future research will focus on optimizing safety and scalability for potential therapeutic applications.
Publication: Paulishak, W., Lyu, J., VanNieuwenhze, M.S., et al. Bugs delivering drugs: Listeria monocytogenes-mediated cytotoxin delivery enhances anti-tumor activity in colorectal cancer. Cell Chemical Biology (2025). DOI: 10.1016/j.chembiol.2025.11.008