In a study published in Science, the researchers described the discovery of certain bacteria inside human pancreatic tumors. The results further indicate that some of these bacteria contain an enzyme that is inactivated by common drugs for the treatment of various cancers, including pancreatic cancer. Using a mouse model, they showed why antibiotic chemotherapy may be significantly better than chemotherapy alone.
The study was conducted in the laboratory of Dr. Ravid Straussman, Department of Molecular Cell Biology, Weizmann Institute of Science, led by graduate student Leore Geller, and Dr. Todd Golub and Michal Barzily, Dr. Broad Institute Dr. Rokini collaborated. Many other collaborators support different aspects of research.
The bacteria found in this group, Straussman explained, live in tumors, even in tumor cells. “Because this topic is so new, we first used different methods to prove that there are really bacteria in the tumor, and then we decided to look at the effects of these bacteria on chemotherapy.”
Researchers from patients with pancreatic cancer Bacteria were isolated from tumors and tested for how they affect the sensitivity of pancreatic cancer cells to the chemotherapy drug gemcitabine. In fact, some of these bacteria make the drug ineffective. Further investigation revealed that these bacteria metabolize drugs, making them ineffective. The researchers were able to find the gene responsible for this bacterium, a gene called cytidine deaminase (CDD). They show that CDD comes in two forms – long and short. Only long-form bacteria of the CDD gene can inactivate gemcitabine. The drug has no significant effect on the bacteria.
This group examined more than 100 human pancreatic tumors to show that these specific bacteria with long CDD do exist in the pancreatic tumor of the patient. They also use a variety of methods to observe bacteria in human pancreatic tumors. This is crucial because bacterial contamination is a real problem in laboratory research.
Oddly, this led to the study of Straussman and his team, the incidence of bacterial contamination was earlier. Straussman and his team have been looking for evidence that normal cells in the cancer environment contribute to chemotherapy resistance. In testing the effects of many normal, non-cancerous human cells on the sensitivity of cancer cells and chemotherapy, they found specific samples of normal human skin cells that make pancreatic cancer cells resistant to gemcitabine. Tracking these causes led the team to accidentally discover the bacteria in these skin cells. “We almost gave up,” Straussman said. “But we decided to follow up.” After revealing how these bacteria degrade the drug, he began to wonder if other bacteria might have similar mechanisms for inactivating drugs, and whether the bacteria May be found in human tumors.
In this study, two groups of bacteria were used for further experiments in a mouse cancer model: a long form of the CDD gene and those whose genes were knocked out. Only mice in the group with a complete CDD gene showed resistance. After treatment with antibiotics, the group also responded to chemotherapy drugs.
A lot of problems still exist, and Straussman and his team are now investigating whether bacteria can be found in other cancer types, and if so, what effects they may have on cancer and their sensitivity to other anticancer drugs. Sexuality needs to be studied, including a new family of immune systems that mediate anticancer drugs. (AFn 206795)