For more than half a century, the war on cancer has been fought mainly with three weapons.

The oldest and most reliable of these has been the simplest — a scalpel, to cut out as much of the mass as possible. Any straggler cancer cells left behind are then scorched with radiation.

Finally, the malignant bits that manage to escape are poisoned with chemicals, although often with serious and unpleasant side effects.

As those three weapons continue to be improved and expanded, overall survival rates improve year by year.

Nearly two out of three Canadians diagnosed with cancer can expect to live at least five years, up from about a 50-per-cent survival rate two decades earlier.

And yet, there’s something missing from this arsenal.

“Slowly but surely we’ve improved our chances of people living longer with better surgical techniques, better radiation techniques, better chemotherapy and more specific chemotherapy along the way,” says Dr. Rosalyn Juergens, a researcher at Hamilton’s Juravinski Cancer Centre.

“But talking to my patients, they often say, ‘Gosh, we kinda thought you guys would hit a home run (by now) and that we could do better.’ ”

Cancer researchers have long believed that a fourth weapon must exist — the human body itself, with the help of the immune system’s soldiers. The immune system has developed some sophisticated weapons to fight off harmful foes, whether foreign or domestic.

Cancer cells are obviously harmful. Over time, they kill the body. Yet when cancer comes calling, for some reason the immune system is tricked into turning a blind eye to the threat.

So why can’t the body’s natural defences mount an attack against these rogue cells? Can the sleeping giant be roused into action?

The answer, it appears, is yes and the implications are massive.

It’s early days yet but immunotherapy — the science of developing treatments that awaken the body’s immune system — is showing signs of turning the tables in the fight against cancer.

“This has changed everything,” says Dr. Jonathan Bramson, a McMaster University researcher and one of Canada’s leading cancer immunology experts. “It’s no longer scientists in a laboratory playing with mice. This is now scientists in a clinic treating patients and getting responses in patients that are unheralded.”

Immunotherapy is the leading edge of a wave of sophisticated new directions in cancer treatment that attack the disease with remarkable precision. It has led to an explosion in the number of options that are available, or soon might be.

Searching with the terms “tumour” and “immunotherapy” on the U.S. National Institutes of Health’s clinical trial registry, there are currently 338 trials actively recruiting patients.

The American Food and Drug Administration is aware of more than 700 cancer drugs of all types in the pipeline. If even a quarter of those make it to the marketplace that would represent a massive influx of new treatments, considering there were only eight new cancer drugs approved in the U.S. in 2014.

At first glance, the numbers reported by clinical trials might not seem impressive. For some new immunotherapies, the average improvement in overall survival might be only a matter of months compared with the previous best option.

But there’s a bigger story hiding in the statistics.

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When some of the treatments have been used against advanced lung cancer and melanoma, up to 20 per cent of the patients have shown a long-term response.

That might not sound like much, but keep in mind that not long ago, the long-term survival rates for final-stage patients would have hovered closer to zero per cent.

“Hopefully, over time, we’re going to be able to afford to be a lot more picky in that a response rate of 20 per cent or living two months longer is just not going to be acceptable,” says Dr. Sebastien Hotte, a medical oncologist and head of the Juravinski Cancer Centre’s Phase I research program. “It has been acceptable in large part because that was as good as it got.”

The solution to better survival rates will likely be a combination of attacks — surgery, radiation and chemotherapy to reduce the bulk of cancerous cells and then an immunotherapy agent to finish the job. Or perhaps a combination of immunotherapy drugs that attack different checkpoints.

“What we’ve learned over the past 35 years in the war against cancer is that you cannot beat cancer with a single line of therapy,” says Bramson. “You’ll only beat it if you come in with multiple lines of attack rapidly before it has a chance to change.”