Bacteria block cancer chemotherapy
Could bacteria be conspiring with cancer to block the action of chemotherapy drugs? According to scientists in Israel, bacteria can get inside tumours, and even inside cancer cells themselves, and then use their own metabolic machinery to protect the tumour by breaking down anti-cancer treatments, like the drug gemcitabine. Chris Smith spoke to Ravid Straussman…
Ravid - They can either come from the bloodstream, the tumours, or because we were exploring pancreatic cancers, they might come from the gastrointestinal tract. We can see them in different methods, we can characterise them, we know which bacteria they are, and we know it can really affect the sensitivity of these cancer cells to chemotherapy.
Chris - How do you know that it is the bacteria that are doing that and it’s not just that the bacteria are there like a bystander because you’ve got abnormal cancer tissue, the bacteria has settled there, and they’ve got nothing to do with the resistance to the drugs?
Ravid - We know in the laboratory that when we take cancer cells and we put chemotherapy on them it’s really easy to kill them but, when we add specific types of bacteria into this culture of cancer cells, the cancer cells become completely resistant to chemotherapy. We found that bacteria can inactivate the drug by cutting it. We also can show with mice models with a cancer and bacteria, the cancer of the mice becomes completely resistant to chemotherapy. But, if you treat these mice with antibiotics, then you can re-sensitise these tumours to chemotherapy.
We do see the same bacteria in human patients. We know that this bacteria have the genes they need to degrade the drug but it’s hard to know what would be the effect of eradicating these bacteria from human tumours.
Chris - So your hypothesis is that people who don’t respond very well to their chemotherapy or develop drug resistance, at least a subset of those patients may well have tumours in which they’ve got bacteria in the tumour and the bacteria are breaking down the chemotherapy drugs so that they don’t kill the cancer cells?
Ravid - Right. We profiled the 113 pancreatic patients and we found bacteria in the majority of them. Bacteria were found between the cells and even inside the cancerous cells and we know, as we said before, that these bacteria have the right capacity to degrade gemcitabine. From here one can only postulate that if you have bacteria inside the cancerous cell and it can degrade gemcitabine, probably it is going to protect the cancerous cells from chemotherapy, but someone would need to do clinical trials in order to validate how important this mechanism really is.
Chris - What specifically where the bugs that you found?
Ravid - We found many bugs, many types of bacteria; some of these you know like e coli or salmonella. The one thing in common to all these bacteria were that they all have a specific enzyme called CDD, which stands for Cytidine Deaminase, and can come in a short or long isoform. We found that only bacteria with the long isoform of CDD can degrade the drug gemcitabine. When we looked into these patients, in the tumours of these patients, we found that many of them have the bacteria of long CDD isoform.
Chris - So that means that particular flavor is capable of breaking down the drug, it’s in those bacteria, so it puts the weapon, the smoking gun, at the scene of the crime and in the hand of the bacterial criminal, doesn’t it?
Ravid - Yes. We also isolated these bacteria and were able to demonstrate that bacteria isolated from pancreatic cancer patients, from the pancreatic tumours, can degrade gemcitabine that we add in the lab to these cells.
Chris - What about doing the experiment where you take tumours and add bacteria to those tumours that have this drug degrading ability, can you then confer on the cancer resistance to the chemotherapy by adding only the bacteria?
Ravid - We did a few of these experiments. We took mice models of cancer, and if we put inside the bacteria with the long CDD isoform, these mice models of cancer become completely resistant to therapy. Then, if we treat them with antibiotics, together with gemcitabine, then we can make these tumours go away. Another type of experiment that we did, we took mice models of cancer, put bacteria inside of them, but we changed one very small piece in the DNA of these bacteria making CDD positive bacteria into these CDD negative bacteria. Then, all of a sudden, these mice are responding to chemotherapy.