An apple a day really DOES keep the doctor away, slashing risk of dying early by 35%

Scientists have discovered exactly how cancer can often come back years later – giving hope of new treatments within a decade.

They have cracked how cancer cells can ‘hide out’ in patients who are dubbed ‘cancer free’ before spreading to other parts of the body.

The study sheds light on how the process – known as latent metastasis – works without the body’s immune system appearing to notice.

It is hoped the discovery, by researchers at New York’s Sloan Kettering Institute, could pave the way for new treatments to stop it returning.


Dr Joan Massagué, head of Memorial Sloan Kettering’s Center for Metastasis Research, said: ‘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.’

These stragglers can go into hiding, only to flare up later somewhere else – a phenomenon termed latent (or dormant) metastasis.

In a paper published today in the journal Cell, Dr Massagué and colleagues describe how they created a new model to understand latent metastasis.

They used it to uncover the mechanisms that underlie cancer’s stealth mode, in ground-breaking research.

‘Understanding latent metastasis is the biggest untapped opportunity to have a major impact on cancer,’ he said.

‘But so far, no one has been able to tackle it.’

Roughly 25 per cent of women with an aggressive form of breast cancer will experience a recurrence of their disease following surgery and chemotherapy.

For lung cancer patients the numbers are even worse with half of patients seeing their cancer come back.

Latent cancer cells are difficult to detect in the body, let alone identify what makes them work.

Srinivas Malladi, a postdoctoral fellow in Dr Massagué’s lab spent six years developing the model and putting it to use.

He 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.

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

He found them hiding in the lungs and kidneys. He called these persistent survivors latency competent cancer (LCC) cells.

With these LCC cells in hand, Dr Malladi could begin to investigate what made them so stealthy.


The 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.

More tantalizing, he found that a proportion of these cells produce a protein – called a WNT inhibitor – that blocks cell division, forcing them into a state of suspended animation.

This slowed-down growth is central to the cells’ ability to survive in the body without detection.

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.

What’s more, most chemotherapies kill only dividing cells, which means that non-dividing LCCs are spared.

Together, these facts explain why most LCC cells are eliminated from the body but a few can survive.

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

The idea that the immune system holds latent cancer in check is not new with the starkest example of this immune surveillance comes from the land of organ transplantation.

Patients receiving an organ from a donor who previously had cancer but was thought to be cured sometimes come down with the disease.

But until now, the mechanism through which latent cancer and the immune system battle it out had remained mysterious.

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, Dr Massagué said.

His team now plan to work with immunologists to study the cells further in the hope of developing potential therapies that could be available within the decade.

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