Can an immune system distracted by post-surgery healing allow previously dormant cancer cells to wake up and cause havoc? Scientists say the science isn’t settled but old drugs may help. 

For years there’s been a question surrounding breast cancer surgery. Twelve to 18 months after surgery there’s a high recurrence rate of cancer. 

It was a dilemma put to the test in mice, the results suggesting the body’s healing response to surgery could be the reason.

The hypothesis is while the body is busy healing a wound, the immune system is less able to keep cancer cells – which had already spread to other areas of the body – dormant. 

Surprisingly, the study found giving the mice over-the-counter anti-inflammatory medicine before and after surgery could reduce the risk.

The study received a fair bit of attention. There was worry from some quarters it may lead to people rejecting important surgery. It also highlighted something as cheap as aspirin could improve patients’ outcomes.

According to University of Otago research fellow Dr Nicholas Fleming, surgery is “almost always the best option”.

His view is the science on surgery and cancer-spread is not settled, and while there may be a risk, not having surgery creates a worse situation.

“If you cut a cancer out early, hopefully you get all of the cancer and that’s the end of it.”

The later the surgery, the greater the chance the cancer has spread.

He describes the question of what causes cancer to spread as a million-dollar question. He puts it down to a collection of mutations.

For the most part, cancer cells do one thing: life revolves around dividing. 

But in the tumour some rebels emerge. Not content to simply divide, they leave home and roam the body. Eventually, these find new spots to colonise. In their new home they begin to divide once more, creating new tumours. 

“That’s why the most important thing in cancer treatment is treating people before they get to that point because after that it becomes very, very hard to save their lives.”

Fleming has been looking at whether existing drugs that are out of patent (and dirt cheap as a result) could help fight cancer spread.

The idea of ‘repurposing drugs’ is an area gaining traction. It was sparked by data showing diabetics taking metformin for their diabetes had a lower rate of cancer than those not taking it.

Since then, hundreds of drugs – not initially designed with cancer in mind – have been associated with effects on cancer.

Association isn’t rock solid proof. The gold standard of proof comes from expensive clinical trials. 

For old drugs with expired patents, this is an issue. There’s no financial incentive for drug companies to fund clinical trials of drugs they won’t profit from.

As a publicly-funded researcher, Fleming is in a position to look at some of the off-patent drugs pharmaceutical companies aren’t interested in.

Rapamycin, used since the 1970s to stop transplants from being rejected, is one drug he’s looked at. He describes it as anti-inflammatory and “anti-migratory”. 

“That drug can stop cells crawling. If you have cells that are migrating, you can stop them with that.”

Fleming, who is also looking at pairing old drugs with the new immunotherapy drugs, is not the only scientist in New Zealand looking at repurposed drugs.

Gillies McIndoe Research Institute executive director Dr Swee Tan’s clinical trial is treating brain cancer with drugs that cost $5 once every three months.

“It’s the worst brain cancer, it’s the most aggressive brain cancer. The median survival is that half the patients will die within 15 months after diagnosis. About half of them will recur within six months of treatment and once they have recurred, about half will die in six months.”

He said 11 people currently in the trial were living longer than expected. The treatment uses blood pressure pills.

“We say cancer is caused by stem cells that have misbehaved and caused cancer.”

Tan uses the analogy of a beehive. A queen bee stem cell makes worker bees that create the tumour, it also makes another queen bee that travels elsewhere in the body and starts another hive.

He found the renin-angiotensin system, which regulates blood pressure and electrolyte balance, also controls the “queen bee”.

“The implication is you might be able to design treatment to control cancer by controlling the cancer stem cells by using medications which control the renin-angiotensin system.”

Delaying clinical proof is funding. 

“New Zealand spends $1 billion a year to treat cancer. That cost is escalating because of very expensive cancer drugs. If the government put aside 1 percent of that – $10 million a year to fund research like this – it will take this whole debate forward. It would allow the work to be done to prove it one way or the other.”

Dr David Jennings, a Bay of Islands GP, thinks there’s a case for not waiting for clinical trials. 

As a GP he’s seen the “fireworks” of cancer spread in patients. He also lost a close friend, and the process of trying to help turned him into an advocate for repurposed drugs. 

His friend’s cancer had spread by the time it was diagnosed, but Jennings believes the repurposed drugs in conjunction with traditional cancer treatments extended his time, and improved its quality.

“Let’s say we’re losing 1000 patients a year, in 10 years that’s 10,000 people. That’s a hell of a lot of people waiting for these studies to be done.”

While clinical trials struggle to get funding, he thinks patients can take a lead, do research and talk to their GP. With repurposed drugs having been around for decades, side effects are well-known. 

“We’re in a good position in New Zealand in terms of being able to repurpose drugs, but it will have to be a patient and doctor decision.”

Read more:

Off-label and untapped – are old drugs new cancer treatments?

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