Discovery of how cancer “hides out” and returns sparks hopes for new treatment

Life scientist researching in the laboratory.

NEW YORK, United States, Wednesday April 6, 2016 – About 25 percent of women with aggressive breast cancer will experience a recurrence of the disease after surgery and chemotherapy. The figures are even worse for lung cancer patients, with roughly half of them seeing their cancer come back.

So the discovery of exactly how cancer can return years later, sparking hope of new treatments to stop it in its tracks, comes as welcome news for millions worldwide.

Scientists at New York’s Sloan Kettering Institute have found out how cancer cells can “hide out” before spreading to other parts of the body in patients who have been dubbed “cancer free.”

The findings of their research explain how the process – known as latent metastasis – can escape without detection by the body’s immune system.

According to Dr Jean Massagué, head of the Institute’s Center for Metastasis Research: “From the time a tumour begins to form until it is surgically removed, it is shedding tumour cells into the body.

“Most of these cells die, but a few may not.”

The surviving cells can go into hiding, only to flare up later elsewhere – a phenomenon known as latent (or dormant) metastasis.

Metastasis is a complex process in which cancer cells leave the original tumour site and migrate to other parts of the body via the bloodstream or the lymphatic system.

In a paper published in the journal Cell, Dr Massagué and colleagues describe how they created a new model to understand latent metastasis, going on to uncover the mechanisms that underlie cancer’s stealth mode.

“Understanding latent metastasis is the biggest untapped opportunity to have a major impact on cancer,” Massagué said. “But so far, no one has been able to tackle it.”

The breakthrough model was developed over a six-year period by Srinivas Malladi, a postdoctoral fellow in Dr Massagué’s laboratory.

Malladi took cells from patients with early-stage breast and lung cancers, which he labelled with a fluorescent tag. He then injected these cells into mice and waited several months.

Almost all of the transplanted cells died, but a few survived.

He found these persistent survivors, which he dubbed latency competent cancer (LCC) cells, hiding in the lungs and kidneys. He then investigated what made these LCC cells so stealthy.

His first clue came from looking at the proteins the cells make. He found that, in this respect, LCC cells behave a lot like stem cells, which divide periodically to repair our tissues.

This stem-like quality helps to explain the LCC cells’ ability to divide and seed distant organs, he said.

But he also found that some of these cells produce a protein called a WNT inhibitor that blocks cell division, forcing them into a state of suspended animation.

By not dividing, the LLC cells become less conspicuous to an important class of immune cells called natural killer (NK) cells that routinely patrol the body, looking for signs of danger.

“The job of NK cells is to sniff out anything that looks funny, like cancer cells, and kill it,” Dr. Massagué said.

But when cells aren’t dividing, they don’t make the molecules that NK cells detect, and so the NK cells ignore them.

Over time, the cells may acquire additional mutations that allow them to escape immune patrol completely and cause a cancer recurrence.

Most chemotherapy treatments kill only dividing cells, which means that non-dividing LCCs are spared, moreover.

Massagué’s team now plans to work with immunologists to study the cells further in the hope of developing potential therapies.

An effective strategy to target latent cancer cells might be to prod them into producing the molecules that would alert the natural killer cells to their presence, he said.

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