How Bacteria Could Protect Tumors From Anticancer Drugs

Cancers have unwitting allies: the healthy cells that surround them. Several groups of scientists have now found that normal cells can inadvertently release substances that shield their malignant neighbors from anticancer drugs. That would explain why even targeted therapies — smart drugs that are meant to hit the specific genetic faults behind various cancers—sometimes stumble right out of the gate. When pitted against isolated cancer cells in laboratory tests, they perform as expected. But when pitted against actual tumors, which enjoy a kind of innate resistance because of the healthy cells around them, the drugs can fail. But at least half of the cells in the human body are not human. Every person is a seething colony of microbes — a collection of tens of trillions of bacteria and other microscopic organisms that live in and on our bodies. And a team of researchers, led by Ravid Straussman from the Weizmann Institute of Science and Todd Golub from Harvard Medical School, have shown that some of these bacteria can also shield tumors from anticancer drugs.

Back in 2012, Straussman and Golub’s team grew dozens of types of cancer cells together with dozens of types of healthy cells, and found hundreds of combinations where the latter protected the former to some degree against chemotherapy. But one particular interaction was especially dramatic: A lineage of skin cells from one individual could completely protect pancreatic cancer cells from gemcitabine — a frontline drug that’s used to treat this stubborn disease. “We could pour on more and more gemcitabine — ten times more than was needed to kill the cancers — and the skin cells from this woman were enough to protect them,” Straussman recalls. Even the liquid in which the skin cells had grown was enough to protect cancers from gemcitabine. Clearly, the skin cells were secreting some kind of chemical that neutralized the drug. But what was it? A protein? A piece of DNA? The team spent years trying to identify the mystery molecule, to no avail. “We did tons of experiments and they led us nowhere,” says Straussman. “It didn’t make any sense.” They finally worked out what was happening when they filtered the liquid — and completely removed its ability to protect tumors. Even filter paper with very large pores, through which most molecules could easily fit, had this effect. That’s when they realized that they weren’t dealing with a molecule at all. They were dealing with a microbe.

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