Novel bacterial therapy approach for treating lung cancer

Columbia Engineering researchers report thatthey have developed a preclinical evaluation pipeline for characterization ofbacterial therapies in lung cancer models. Their new study, published December13, 2022, by Scientific Reports, combines bacterial therapies with othermodalities of treatment to improve treatment efficacy without any additionaltoxicity. This new approach was able to rapidly characterize bacterialtherapies and successfully integrate them with current targeted therapies forlung cancer.

Lung cancer is the deadliest cancer in theUnited States and around the world. Many of the currently available therapieshave been ineffective, leaving patients with very few options. A promising newstrategy to treat cancer has been bacterial therapy, but while this treatmentmodality has quickly progressed from laboratory experiments to clinical trialsin the last five years, the most effective treatment for certain types ofcancers may be in combination with other drugs.

"We envision a fast and selectiveexpansion of our pipeline to improve treatment efficacy and safety for solidtumors," said first author Dhruba Deb, an associate research scientist whostudies the effect of bacterial toxins on lung cancer in Professor Tal Danino'slab in Biomedical Engineering, "As someone who has lost loved ones to cancer, Iwould like to see this strategy move from the bench to bedside in the future."

The team used RNA sequencing to discover howcancer cells were responding to bacteria at the cellular and molecular levels.They built a hypothesis on which molecular pathways of cancer cells werehelping the cells to be resistant to the bacteria therapy. To test theirhypothesis, the researchers blocked these pathways with current cancer drugsand showed that combining the drugs with bacterial toxins is more effective ineliminating lung cancer cells. They validated the combination of bacteriatherapy with an AKT-inhibitor as an example in mouse models of lung cancer.

"This new study describes an exciting drugdevelopment pipeline that has been previously unexplored in lung cancer – theuse of toxins derived from bacteria," said Upal Basu Roy, executive director ofresearch, LUNGevity Foundation, USA. "The preclinical data presented in themanuscript provides a strong rationale for continued research in this area,thereby opening up the possibility of new treatment options for patientsdiagnosed with this lethal disease."

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

Reference:

Dhruba Deb et al,Design of combination therapyfor engineered bacterial therapeutics in non-small cell lung cancer,ScientificReports,DOI: 10.1038/s41598-022-26105-1