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Thanks to a chance discovery, researchers have uncovered one reason why chemotherapy drugs sometimes fail. It turns out that bacteria inside cancer cells can destroy some drugs, rendering them useless.
The finding may explain why so few people with pancreatic cancer are successfully treated with the drug gemcitabine; bacteria that can destroy gemcitabine were discovered in three-quarters of biopsies from 113 people with pancreatic cancer.
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The drug is also used to treat colon and bladder cancer, and so the same effect may play a role in people with those cancers too, says the team behind the findings.
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Ravid Straussman at the Weizmann Institute of Science in Israel and his team made the discovery after getting puzzling results while they were investigating why healthy cells become “accomplices” to cancer cells, somehow helping them to resist drugs. They couldn’t explain why one particular group of skin cells prevented gemcitabine from killing neighbouring cancer cells.
Drug degraded
Straussman and his colleague Leore Geller noticed that the skin cells were infected with Mycoplasma bacteria, but initially dismissed it as contamination. “I almost gave up on the project,” says Straussman.
In fact, it turns out that the bacteria destroy gemcitabine. “We found that the bacteria internalise then degrade the drug, deactivating it,” says Straussman. It does this by producing a “long form” of an enzyme called cytidine deaminase.
After analysing 113 samples of pancreatic cancer tissue, they found 86 were infected with types of bacteria that could make the long form of the enzyme. These included very common bacteria such as E. coli and salmonella.
Of 2674 bacterial species – some of which are known to live in the human body – tested subsequently, 11 per cent could make the long form of the enzyme. Almost half couldn’t make the enzyme at all, and the remainder made the short form, which cannot degrade the drug.
The discovery tallies with findings from other labs that bacterial infections can hamper chemotherapy.
Antibiotic resistance
In further experiments, Straussman showed that antibiotics stopped bacteria with the long form from destroying gemcitabine.
“Using antibiotics alongside standard cancer drugs certainly deserves further investigation,” says Yi Xu of the Health Science Center at Texas A&M University, who previously discovered that bacteria can speed up the growth of colon cancer. “Treatment of cancer in the future should take into consideration the bacterial characteristics of the patients.”
Straussman cautions that this strategy could bring complications, as people would need to take antibiotics for long periods of time, which could drive the emergence of antibiotic-resistant bacteria.
“We believe there may be better approaches, such as developing drugs to specifically block the activity of the enzyme that destroys gemcitabine,” he says. “This would minimise the effect of the bacteria without risking generation of antibiotic-resistant bacteria.”
Straussman’s team are now investigating how bacteria sabotage another anticancer drug called oxaliplatin. “We don’t think our gemcitabine discovery is an isolated phenomenon,” he says.
Journal reference: Science, DOI: 10.1126/science.aah5043
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