The Riddle of Bacteria and Cancer
Bacteria can be friend or foe—or both. Researchers are looking at bacteria to boost the effectiveness of cancer treatments, even if they don't fully understand how the tiny organisms work.
By Stephen Ornes
The human body teems with bacteria. These micro-organisms live on the skin, in mucus membranes, on the eyes and in the gut, among other places. The large intestine alone hosts up to 1,000 different species. According to a study published in the January 28, 2016, Cell, an average human hosts about as many bacterial cells as the cells that make up skin, bone, organs and the rest of the body.
“The way that a host animal’s body interacts with bacteria is fundamental to basic survival,” says Susan Erdman, a researcher who studies comparative medicine at the Massachusetts Institute of Technology in Cambridge. So it’s not surprising that researchers have long studied the interaction between bacteria and cancer.
Depending on the species and location, bacteria may be harmful or protective. Or both: It’s been known for decades that infection with a type of bacteria called Helicobacter pylori may result in ulcers and can lead to stomach cancer in some patients. And yet a large study published in 2008 concluded that patients infected with some strains of H. pylori are at reduced risk of developing esophageal cancer.
H. pylori isn’t the only type of bacteria associated with cancer. Recent investigations suggest that bacteria in the gut also play a role in a patient’s response to many conditions, not only gastrointestinal diseases but other cancers, including melanoma. In addition, there is growing support for the idea that bacteria can be used and modified to help patients—to develop new anti-cancer drugs, to boost the efficacy of existing drugs or to stimulate the immune system to better attack cancer cells.
“We know bacteria can cause cancer. But more than a decade ago, we became interested in how bacteria might instead prevent or treat cancer,” says Erdman. “We want to harness the beneficial effects of bacteria in anti-cancer therapies while minimizing the damaging side effects that infectious agents can have.”
Erdman has spent years studying bacteria and cancer and is optimistic that a deep understanding of how bacteria interact with the immune system will drive new treatments and prevention strategies.
Treating Cancer With Bacteria
More than 200 years ago, physicians observed a connection between bacterial infections and tumor shrinkage—though they didn’t understand the link between the two. In 1813, French physician Arsène-Hippolyte Vautier reported that tumors got smaller in patients who developed severe infections from Clostridial bacteria. About 50 years later, a woman with an inoperable sarcoma visited German physician Wilhelm Busch, who exposed her to erysipelas, a skin infection characterized by high fever and raised red rashes. (Scientists now know that erysipelas is a bacterial infection, but Busch was not aware of that.) Busch tried the treatment because, in previous years, he had observed tumors shrinking in a patient with erysipelas. His sarcoma patient’s tumor regressed, but she died nine days after infection.
In 1891, a young American surgeon named William Coley identified a head and neck cancer patient whose tumor disappeared after a severe erysipelas infection. He suspected, as researchers now believe, that the Streptococcus pyogenes bacteria that cause erysipelas triggered an immune response in the patient’s body that attacked both the infection and nearby cancer cells. Encouraged, he began treating more patients who had no other treatment options with Streptococcus pyogenes, with some success. “Coley’s toxins” remained a cancer treatment option into the middle of the 20th century, when the U.S. Food and Drug Administration (FDA) declared the controversial therapy could not be continued without extensive clinical trials to evaluate its safety and effectiveness. Studies in the 1970s ultimately failed to demonstrate a survival benefit from the treatment.
In the 1960s and 1970s, reports of guinea pig experiments described startling results when the animals’ tumors shrank or vanished after exposure to a bacterium called Bacillus Calmette-Guerin, or BCG. The bacteria, like Coley’s toxins, were believed to trigger an anti-cancer response in the immune system.
Inspired by the guinea pig studies, in the mid-1970s, Canadian urologist Alvaro Morales applied to the National Cancer Institute of Canada for funds to pursue BCG research in bladder cancer patients. His application was denied. He remembers one review slamming the proposal, noting that BCG, which is related to the bacterial strain that causes tuberculosis, was ineffective and dangerous.
Disappointed but undaunted by the rejection, Morales secured funding elsewhere. In the years that followed, he found BCG reduced the risk of recurrent bladder cancer in patients who had undergone bladder surgery. In 1989, the FDA approved BCG for noninvasive bladder cancer, and it remains a standard post-surgery treatment for those patients, even though about 30 percent of them don’t respond to the therapy and its side effects can be serious.
“I’ll never forget that assessment, but the reviewer proved to be wrong over time,” says Morales, who retired from Queen’s University in Kingston, Ontario, in 2004. Now, he says, “there seems to be a renaissance of interest in using bacteria” to treat cancer, as recent studies suggest some bacterial strains may improve treatment efficacy or help with side effects.
Balancing the Good and the Bad
Bacteria and the immune system are in constant communication, says Erdman. These interactions help determine whether a person has good health or develops disease, and it can be useful, if simplistic, to think of bacteria as being good or bad. Maintaining a strong population of good bacteria, says Erdman, is a sound strategy for keeping disease at bay.