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A research team from the University of Waterloo is pioneering a novel cancer treatment strategy that utilizes engineered bacteria to target and eliminate solid tumors from the inside out. This innovative approach centers on the bacterium Clostridium sporogenes, which thrives in oxygen-deprived environments often found at the core of malignant tumors.
Solid tumors typically have a complex internal structure, with their centers becoming hypoxic (lacking oxygen) as they grow. This environment is ideal for C. sporogenes, which can flourish and consume the nutrients present in these areas. Researchers aim to enhance the bacterium’s ability to survive as it approaches the tumor’s outer edges, where oxygen levels increase and conditions become less favorable.
To achieve this, the Waterloo team has introduced a gene from a related bacterium that increases oxygen tolerance in C. sporogenes. However, controlling this gene’s expression is crucial to prevent the bacteria from surviving in oxygen-rich environments outside the tumor. The researchers employed a natural communication mechanism called quorum sensing, which allows the bacteria to monitor their population density. This system activates the oxygen-resistant gene only once a sufficient number of bacteria are present, ensuring their survival within the tumor while minimizing risks elsewhere in the body.
The project is grounded in synthetic biology principles, where the team constructs biological systems akin to electrical circuits using DNA components that perform specific functions. Past studies have demonstrated the feasibility of modifying C. sporogenes for oxygen tolerance and successfully utilizing quorum sensing to regulate gene expression.
Next steps for the research team involve integrating the oxygen-resistant gene with the quorum-sensing mechanism and conducting preclinical trials against tumors. This project emerged from the efforts of Ph.D. student Bahram Zargar, under the guidance of professors Brian Ingalls and Pu Chen, along with contributions from former doctoral student Sara Sadr. The team is collaborating with CREM Co Labs, an environmental microbiology company based in Toronto.
While the research is still in its early phases and preclinical outcomes do not always predict human trial results, the concept of harnessing bacteria to exploit the unique characteristics of tumors presents a promising avenue for cancer treatment.
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