Bacteria in Tumors Can Thwart Chemotherapy, Israeli Researchers Say

The microbes apparently suck in the cancer drug, cut off some of the molecule and totally inhibit its activity, hampering the fight against pancreatic cancer, Weizmann scientists say

Bacteria (green) within cancerous tumor cells, from a 2017 study by researchers at the Weizmann Institute of Science.
Leore Geller

Bacteria in cancerous growths may impair the effectiveness of chemotherapy given to patients with pancreatic cancer, according to a study by researchers at the Weizmann Institute of Science.

The bacteria studied neutralize a common chemotherapy drug that is used to treat various cancers, according to research just published in the journal Science.

Chemotherapy is usually exhausting and full of side effects, and it isn’t always successful. Pancreatic cancer is particularly deadly because it progresses fast and is usually discovered at an advanced stage. Few people recover from it. In Israel, some 500 people are diagnosed with pancreatic cancer each year.

The study, which was led by research student Leore Geller, in cooperation with Dr. Todd Golub and Michal Barzily-Rokni from the Broad Institute at MIT, shows that the microbes that live in tumors can play a significant role in the failure of chemotherapy.

Dr. Ravid Straussman of Weizmann’s Molecular Cell Biology Department, in whose lab the study was done, has for years been studying the resistance of tumors to chemotherapy and other treatments.

But the question of bacteria came up by chance, he says. It 2012, he and his colleagues published a study in the journal Nature showing how in some cases healthy cells in tumors could cause resistance to chemotherapy.

One model also examined the influence of the chemotherapy drug Gemcitabine on pancreatic cancer cells that had healthy cells alongside them. But those findings showed that the healthy cells had no influence on the therapy except in one case: when a skin cell found in a sample was tainted with the bacteria mycoplasma.

“This is bacteria known to contaminate laboratory cultures, which is why we suspected that this was the case, and we were talking about a contaminated culture,” Straussman said.

The researchers examined how the bacteria could protect cancer cells from chemotherapy, and whether bacteria could be found inside pancreatic tumors. They later decoded the bacteria’s modus operandi.

“It seems that the microbes suck in the Gemcitabine, cut off some of the molecule and thus totally inhibit its activity,” Straussman said. “The bacteria themselves are not harmed by the drug.”

The scientists then discovered that 11.4 percent of all the bacteria checked contained the version of the protein that can neutralize the drug. They also checked to what degree such bacteria were found in pancreatic tumors.

The problem bacteria were found in 76 percent of the 113 samples from pancreatic tumors. During the last stage the researchers showed that when mice with tumors were given antibiotics along with Gemcitabine, their response to treatment was better.

According to Straussman, one can assume that the many bacteria found in people’s digestive systems may have an effect on chemotherapy. “There’s a whole world here whose surface we are only beginning to scratch,” he said.

He added, however, that using antibiotics routinely with chemotherapy is not the solution.

“Broad use of antibiotics could cause the appearance of new strains of bacteria that are resistant to chemotherapy and endanger patients,” he said. “Moreover, such antibiotic treatment could have other unexpected effects.