Salmonella May Be Vehicle for Making Prostate Cancer Therapies More Effective

Salmonella May Be Vehicle for Making Prostate Cancer Therapies More Effective

A non-toxic Salmonella strain may be the key to treating a variety of cancers, including prostate cancer, according to a recent study published in PLOS One.

The study, “Salmonella Bacterial Monotherapy Reduces Autochthonous Prostate Tumor Burden in the TRAMP Mouse Model2,” used a mouse model of prostate cancer to show that a modified Salmonella typhimurium strain can penetrate the cell barrier of tumors and replicate inside them.

“Salmonella strains have a natural preference for infiltrating and replicating within the cancer cells of a tumor, making the bacteria an ideal candidate for bacteriotherapy,” Robert Kazmierczak, a senior investigator at the Cancer Research Center and a post-doctoral fellow in Division of Biological Sciences at the University of Missouri College of Arts and Science, said in a press release. “Bacteriotherapy is the use of live bacteria as therapy to treat a medical condition, like cancer.”

The idea of using bacteriotherapy for treatment of cancer was originally proposed more than a century ago, when researchers found that bacteria, pretreated with heat, could inhibit cancer growth.

Attenuated Salmonella candidates have been extensively studied for targeted treatment of cancer, but recent clinical trials have shown excessive toxicity when Salmonella was used at high doses.

Researchers have since focused on a way of lowering the toxicity of the Salmonella strain, while preserving its unique tumor targeting and infiltration behavior.

In this study, researchers used a Salmonella strain, called CRC2631, that was stored in a test tube at room temperature for over 50 years. As a result, the bacteria acquired a number of genetic mutations that allowed them to survive for long periods under nutrient limiting conditions. Importantly, the resulting modified strain did not change its tumor-targeting capacity, but showed a dramatically reduced toxicity.

To test it, the team administered CRC2631 directly into the circulatory system of mice model of prostate cancer called TRAMP.

“We found that the mice tolerated the treatment well and when examined, their prostate tumors decreased by about 20 percent compared to the control group,” Kazmierczak said, although noting that the treatment did not stop tumor progression and is not likely to work as a sole therapy. But it may aid in the administration of other therapeutics, like chemotherapy.

“One of the most remarkable aspects of Salmonella is its ability to target, spread and persist inside the tumor,” he said. “We are taking advantage of this ability by using Salmonella to carry or generate effective chemotherapeutic drugs, concentrating them at and throughout the tumor. The goal of this treatment is to develop a bacterial vector that can destroy the tumor from the inside out and reduce the amount of side effects endured by patients with cancer.”

The tested Salmonella strain originated from the Demerec collection, a collection of over 20,000 mutant Salmonella strains assembled by geneticist Milisav Demerec.

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Inês Martins holds a BSc in Cell and Molecular Biology from Universidade Nova de Lisboa and is currently finishing her PhD in Biomedical Sciences at Universidade de Lisboa. Her work has been focused on blood vessels and their role in both hematopoiesis and cancer development.

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