Effective cancer therapies rely on identifying and exploiting the differences between normal and malignant tissues. These differences can be molecular, such as genetic mutations, or physiological, as seen in the unique characteristics of tumors. Malignant solid tumors are typically structured with a viable outer rim and a necrotic inner core. While most current treatments focus on the well-vascularized outer rim, the inner hypoxic core remains an underexplored target. This core is distinct from normal tissue due to its poor vascular supply, resulting in a lack of oxygen and nutrients. The absence of functional blood vessels also impairs the clearance of toxic cellular debris, creating a low pH environment. While inhospitable to most human cells, this environment is ideal for the growth of certain anaerobic bacteria.

One such bacterium is Clostridium novyi-NT, an anaerobic strain identified after extensive screening for its ability to germinate and colonize tumors in mouse models. Our earlier research revealed that this bacterium secretes a membrane-disrupting protein, which can be leveraged to enhance the effectiveness of cancer drugs. When bacterial spores are administered intravenously, they germinate specifically within the hypoxic tumor core and secrete the protein. A subsequent intravenous dose of cancer drugs, encapsulated in lipid particles, leads to these lipid particles breaking apart in the tumor’s vicinity due to the secreted protein, releasing the drug precisely where it is needed. This approach highlights the potential of anaerobic bacteria to improve the precision of cancer drug delivery, addressing the relatively low specificity of many current treatments.

We are currently exploring additional anaerobic bacteria and advanced engineering strategies to further enhance the safety and efficacy of this innovative cancer therapeutic approach.