Drug-busting bacteria may be the culprit behind resistant tumors


Debugging a cancer therapy

Bacteria (in green) inside a pancreatic cancer cell of the AsPC1 pancreatic cancer cell line. The nucleus of the cancer cell is in blue. Photo Credit: Leore Geller

Researchers have found a new culprit responsible for drug resistance in cancer. It’s not the cancer cells this time, but bacteria lurking around within the tumor. The study, led by Ravid Straussman at the Weizmann Institute of Science, Israel, was published in Science in September 2017. These findings bring a new perspective to cancer chemotherapy and kindle the idea that addition of an antibiotic to the drug regimen may compel resistant tumors to succumb to the treatment.

The researchers observed that when some types of cancer cells were grown together, their resistance to gemcitabine, an anticancer drug used against pancreatic, lung, breast, ovarian and bladder cancer, increased.

They suspected that the cancer cells secreted some chemical that inactivated the drug, and hence, filtered the culture medium to capture the chemical. Interestingly, they noted that the cells became susceptible to gemcitabine after passing the medium through the filter that would permit small molecules but retain microorganisms. Their suspicion now turned towards bugs, and on further probing, the team established that the cancer cells were contaminated with the bacteria Mycoplasma hyorhinis, which was found guilty of metabolizing and inactivating gemcitabine.

Studies in mice confirmed the findings; tumors infected with M. hyorhinis were more resistant to gemcitabine compared to those without the bacteria. The scientists found that the gene CDDL, which codes for the bacterial enzyme cytidine deaminase, was responsible for the drug-inactivating effect of the bacteria. Upon searching for the presence of this gene in 2,700 types of bacteria they found that it was fairly common, and most of the bacteria carrying this gene belonged to the Gammaproteobacteria group.

An example of an experiment where bacteria (green) and cancer cells (red) are co-cultured. Photo Credit: Leore Geller

In another experiment, the team injected E.coli bacteria containing the CDDL gene in tumor-carrying mice and treated the mice with either gemcitabine alone or in combination with the antibiotic ciprofloxacin. Both bacteria and tumor cells were labeled with fluorescent markers. In the mice that received the combination therapy, bacteria disappeared and the tumors decreased in size, whereas tumor size increased rapidly in the only-gemcitabine group.

To validate that these findings were relevant in humans, 113 pancreatic tumor samples (collected during surgeries) and 20 non-cancerous pancreas samples (from organ donors) were collected and analyzed for the presence of bacteria. For the cancer samples, 86 of 113 tested positive for bacteria, mainly Gammaproteobacteria, compared to three of 20 non-cancerous samples that showed the presence of bacteria.

Albeit promising, these findings will need extensive studies in humans before possible application as a clinical practice.

The original paper can be accessed here.

Source: ArsTechnica