Scientists are always cautious about giving false hope, and at the turn of the decade, many cancer researchers had given up hope of a true cure.
But then, to the surprise of almost everyone, a stream of research that was long overlooked radically transformed cancer treatment.
These new treatments rely on cloning and genetic editing, treatments that retain a whiff of sci-fi even as they become established lifesavers. They are known as immunotherapy.
But in some cases, these new treatments are beginning to look "scarily like a cure", says Professor David Thomas, head of cancer research at the Garvan Institute of Medical Research.
Says Darren Saunders, a UNSW cancer researcher: "The way my clinical colleagues describe it to me is (that it's) the biggest transformation in the way we treat cancer in their careers."
It has made an enormous difference to patients who might otherwise have given up hope.
Warren Penna first noticed something was amiss when a large freckle on his right shoulder started to change shape. Then it darkened and began to bleed. The retired horticulturist went to a number of specialists before he was finally diagnosed with melanoma in 2014.
He had the cancer removed from his shoulder at The Alfred, but earlier this year, the 54-year-old Footscray man was diagnosed with throat cancer. As specialists conducted scans of his body, they discovered melanoma tumors in his lungs, liver, armpit, and brain.
"When I saw the scans I was certain a dead man," Mr. Penna said.
Doctors decided to target the melanoma first and the last eight months have been a blur of radiation treatments and surgery.
But it is the immunotherapy that Mr. Penna is undergoing at Peter MacCallum, which involves fortnightly injections of antibodies Nivolumab and Ipilimumab, that has garnered the most remarkable results.
In a matter of months, the largest tumor in his lung has shrunk from 4.5 centimeters to 2 centimeters and specialists remain optimistic. His immunotherapy treatment will continue until mid-2022.
"It can be really tough at times because you are constantly thinking about your own mortality," Mr Penna said.
"But I feel so incredibly grateful I am able to get this treatment here in Australia and that is available on the Pharmaceutical Benefits Scheme because I have no doubt I would be dead right now without it."
Immunotherapy is known for its severe side-effects and Mr. Penna, who is also due to start radiation next week for his throat cancer, struggles with overwhelming fatigue and sometimes breaks out in a rash.
"I count myself very lucky though because so many others have really significant side-effects like diarrhea and nausea," he said.
Cancer develops when a normal cell’s DNA mutates; often this is because it was exposed to a carcinogen like sunlight, but sometimes there is no cause at all. Just bad luck.
Our immune system is designed to sniff out and kill these mutated cells, but sometimes, the DNA mutation changes the cell in a way that makes it invisible to our immune system. Unchecked, the cell multiplies into a lethal tumor.
For the past 200 years, our treatments for cancer have been crude: surgery to remove the tumor; radiation to kill it; and broad poisons that kill the cancer but often the patient as well.
And then, almost overnight, everything changed.
In the '80s and ‘90s, scientists discovered immune checkpoints, tiny molecular flags that cells run-up to mark them as friendly, so the immune system does not kill them.
They then discovered some cancers were covered in these flags, making them completely invisible to the immune system.
What if, the scientists thought, you could get rid of those flags?
"Initially, people were pretty skeptical of this idea. It was pretty unpopular," says Professor Doug Hilton, head of the blood cancer lab at the Walter and Eliza Hall Institute.
Independently, other labs had developed monoclonal antibodies. These are human immune molecules, made by cloned human immune cells living in a laboratory dish and specifically engineered to stick to a certain part of a cell.
With a tweak, the antibodies could gum over the checkpoints on cancer cells. Suddenly, they were visible to the immune system, which killed them.
The first immune checkpoint inhibitor, the skin cancer drug Yervoy, was approved in Australia in 2011. Lung cancer drug Keytruda – which Professor Hilton labels as one of the most important cancer medicines of the decade – was approved four years later, and came on the Pharmaceutical Benefits Scheme at the start of December 2019.
"They have been absolutely transformative," says Professor Thomas.
A 2015 review of clinical trials of Yervoy for melanoma found more than 20 percent of those treated were alive 10 years later and showing no sign of the disease. Before the treatment, the long-term survival rate was less than 10 percent.
Keytruda treatment has led to complete remission for 22 percent of patients with Hodgkin’s lymphoma in one clinical trial; in another, it cut the risk of death by 40 percent compared to conventional chemotherapy.
Importantly, the effect of the checkpoint inhibitors appears long-term. Even after therapy stops, the immune system is still capable of spotting and killing any new cancers that arise.
"It appears to be a cure for some individuals," says Professor Thomas.
In 2011, as everyone was celebrating Yervoy’s success, word started to filter out about remarkable results in Philadelphia.
An American team had completely cured a seven-year-old of a lethal childhood cancer leukemia, using a new treatment called CAR-T.
That child, Emily Whitehead, is now 14. The cancer has not returned.
CAR-T works in reverse to checkpoint inhibitor therapy. A patient’s own immune cells are drawn from the blood and placed in a test tube.
A genetically modified virus is used to edit the DNA of those immune cells, giving them the ability to seek and kill the patient’s tumor.
When CAR-T works, it works extraordinarily well. One clinical trial led to the complete eradication of cancer in more than half the study participants.
Most excitingly, if the technique works, it could be used for almost any form of cancer. All the doctors would need to do is to tweak the T cell’s DNA to target the cancer in question.
The challenge, says Dr. Saunders? "At the moment it costs half a million dollars per patient."
This is the next step. Bringing down the cost of immunotherapy, while also continuing clinical trials to see what other cancers it will work on.
But for the first time, a durable cure for cancer actually seems within our grasp.
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