Lung cancer, conceptual image

A combination of bacterial therapy with other treatment modalities may improve cancer treatment efficacy without additional toxicity, according to a report from Columbia Engineering researchers. They have developed a new approach for preclinical evaluation of bacterial therapies in lung cancer models. Using this approach, they were able to rapidly characterize bacterial therapies that could be successfully combined with targeted therapies for lung cancer.

Their study appeared this month in Scientific Reports.

“We envision a fast and selective expansion of our pipeline to improve treatment efficacy and safety for solid tumors,” said first author Dhruba Deb, an associate research scientist who studies the effect of bacterial toxins on lung cancer in Professor Tal Danino’s lab in Biomedical Engineering.

Lung cancer is the second most common cancer worldwide, and there were more than 2.2 million new cases of the disease in 2020, according to the World Cancer Research Fund International. Further, many currently available therapies are relatively ineffective, leaving patients with very few options. In the US, the five-year survival rate for lung cancer is just 18.6%.

Bacterial therapy is a promising new strategy to treat cancer. As Sedighi et al. wrote in 2019, “Bacteria alone can act as potent antitumor agents. Another remarkable feature of bacteria is their ability to be genetically engineered to alter their ability to synthesize and release specific compounds, and tailor their metabolic pathways.”

But while this treatment modality has quickly progressed from laboratory experiments to clinical trials in the last five years—there are dozens of trials ongoing, the most effective treatment for certain types of cancers may be in combination with other drugs, according to Danino, whose lab is at the forefront of using bacterial therapy for cancer.

This Columbia team used RNA sequencing to discover how cancer cells were responding to bacteria at the cellular and molecular levels. They screened 10 engineered bacterial toxins across six non-small cell lung cancer patient-derived cell lines and identified theta toxin as a promising therapeutic candidate.

Next, they developed a hypothesis about which molecular pathways of cancer cells were helping the cells to be resistant to the bacteria therapy. To test their hypothesis, the researchers blocked these pathways with current cancer drugs and showed that combining the drugs with bacterial toxins is more effective in eliminating lung cancer cells. They validated the combination of bacteria therapy with an AKT-inhibitor as an example in mouse models of lung cancer.

“This new study describes an exciting drug development pipeline that has been previously unexplored in lung cancer—the use of toxins derived from bacteria,” said Upal Basu Roy, executive director of research, LUNGevity Foundation, USA.

He added that, “The preclinical data presented in the manuscript provides a strong rationale for continued research in this area, thereby opening up the possibility of new treatment options for patients diagnosed with this lethal disease.”

Deb plans to expand his strategy to larger studies in preclinical models of difficult-to-treat lung cancers and collaborate with clinicians to make a push for the clinical translation.

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