Weizmann researchers discover how bacteria can hinder chemotherapy
Oncologists have long been puzzling over why chemotherapy may be effective in some cancer patients and ineffective in others. Researchers at the Weizmann Institute of Science in Rehovot have now discovered one reason for this in human pancreatic malignancies: The presence of a certain bacteria can hinder chemotherapy.
The research was conducted in the lab of Dr. Ravid Straussman of the Molecular Cell Biology Department, led by his graduate student Leore Geller and conducted in collaboration with Dr. Todd Golub and Dr. Michal Barzily-Rokni of the Broad Institute at the Massachusetts Institute of Technology. It was published last week in the journal Science.
The Rehovot-led team showed that some of these bacteria contain an enzyme that inactivates a common drug used to treat various cancers, including pancreatic cancer. Working with mouse models of cancer, they showed how treatment with antibiotics on top of chemotherapy may be significantly superior to treatment with chemotherapy alone.
The bacteria, explained Straussman, live within the tumors and even within the tumor cells. “Because the topic is so new, we first used different methods to prove that there really were bacteria inside the tumors. Then we decided to look at the effect that those bacteria might have on chemotherapy.”
The researchers isolated bacteria from the tumors of pancreatic cancer patients and tested how they affect the sensitivity of pancreatic cancer cells to chemotherapy drug Gemcitabine. Indeed, some of this bacteria kept the drug from working. Further investigation showed that these bacteria metabolize the drug, making it ineffective. The researchers were able to find the bacterial gene responsible for this, called cytidine deaminase (CDD). They demonstrated that CDD comes in two forms – a long and a short form. Only bacteria with the long form of the CDD gene could deactivate Gemcitabine. The drug had no apparent effect on the bacteria.
The group examined over 100 human pancreatic tumors to show that these particular bacteria with long CDA actually live in the patient’s pancreatic tumors. They also used multiple methods to visualize the bacteria inside human pancreatic tumors. This is crucial, they said, since bacterial contamination is a real issue for lab studies.
In the present study, further experiments in mouse models of cancer were conducted with two groups of bacteria – those containing the long form of the CDD gene and those in which the gene had been knocked out. Only the group with the CDD gene intact exhibited resistance when the drug was given to the mice. After treatment with antibiotics, this group also responded to the chemotherapy drug.
Although many questions still remain, Straussman and his team are now looking at whether this bacteria may be found in other cancer types and, if so, what effects they might have on the cancer and its sensitivity to other anti-cancer drugs – including a novel family of immune-mediated anti-cancer medications.