How Close Are We To Curing Cancer? A Timeline


 
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By Anna Mage

Twenty-six years ago, Prof Charles Swanton was in his first year of medical school when his father, Howard, was diagnosed with diffuse large B-cell lymphoma, a cancer of B-cells, a type of white blood cell responsible for producing antibodies.

"It was all doom and gloom," he remembers. "We were sure we going to lose our father. But that was 1991, and he is still alive and working in the NHS."

With radiation and combination chemotherapy, he survived and was cured. "It was a real eye-opener about what prior research had already achieved and what people can do when they come together. I thought, 'Right, I want to be involved in cancer research, I want to do something that makes a difference'."

Since beginning his PhD in 1996 at the Imperial Cancer Research Fund Laboratories in Lincoln's Inn Fields, a site that would later become the Crick Institute, Prof Swanton has published 146 papers about cancer evolution and genetics. It's when he talks about the subject of his 147th paper, published in the journal Science two weeks ago, that this 44-year-old's face really lights up.

Hailed as one of the biggest breakthroughs in cancer research for decades, Prof Swanton and his team identified the "Achilles heel" of cancer that could potentially harness the patient's own immune system to create new bespoke treatments for advanced or returning cancers.

Essentially, they found that cancers held within them the seeds of their own destruction because they all carried "flags" that could be spotted by the immune system, no matter how much they mutated (and cancers mutate often and quickly).

This discovery paves the way for new cancer treatments that use the patient's own immune cells, grown in the lab and re-administered for individualised treatment.

Just last week, it was revealed that scientists had built nanoparticle factories that acted as "Trojan horse" vessels which, once injected, could ferry chemotherapy drugs direct to cancers. In separate research on 257 women, scientists showed that two drugs, lapatinib and trastuzumab, when used together could shrink or even eliminate breast cancer tumours in less than two weeks. However, while exciting new research continues, and over the past 40 years survival rates have doubled, many cancers remain incurable.

The reason current treatments are often unsuccessful is because cancer evolves and mutates rapidly, tricking the immune system and the drugs being administered to treat it.

For example, a drug such as Herceptin, used to treat the 15-25 per cent of women with breast cancer who have HER-2 positive cancers, targets some tumour cells, but can still leave behind a reservoir of cells that can potentially grow and become resistant to treatment.

The same problem of drug resistance occurs with most such cancer drugs, known as "targeted therapies".

"It's very like bacterial resistance," says Prof Swanton. "When you give an antibiotic, bacteria develop resistance. When you give a chemotherapy drug, cancers develop resistance and stop responding to them."

THE POTENTIAL SOLUTION - THE BODY'S OWN IMMUNE

Prof Swanton's team, based at the Crick Institute and University College London and funded by Cancer Research UK, found that even when it had mutated, a cancer still carried signature molecules that didn't change and could be spotted by the immune system's disease-fighting T-cells.

"As cancers evolve, they develop mutations and these mutations can, in some cases, be seen as flags on the surface of the tumour cells by the immune system as being abnormal and so the immune system will try to tackle those flags," says Prof Swanton.

His team took numerous biopsies from two patients with lung cancer and found evidence that their immune systems recognised the flags on the surface of every tumour cell.

"I hope this is a breakthrough, but we won't know until we have treated the first patient," says Prof Swanton, who specialises in lung cancer, which kills 45,000 people a year.

"Around 85 per cent of the patients I see present with advanced disease and we will not be able to cure them - that is something we have to get to grips with."

THE FUTURE VISION - INDIVIDUALISED CANCER THERAPIES

Though preliminary, the potential of such a discovery is momentous.

"Because no two tumours are the same, we want to find a way to hit those flag proteins by using the body's own defences to do it individually for each patient."

Theoretically, this means oncologists could look at the genetic profile of a tumour and locate the "flags" that are recognised by an individual's immune system, then engineer billions of these special immune T-cells and transfer them back into the patient "so they have more of their own immune cells to fight their own cancers", says Prof Swanton.

The first safety trials could happen within two years, followed potentially by the treatments of the first patients (though it could take 10-15 years before such treatment became routine therapy). It's ambitious, he says, but important because the one-size-fits-all approach we currently have is flawed because drug resistance will always occur in some patients.

The findings could also be used to create a vaccine to increase the body's defences. "In this scenario, which is probably a more likely one, we would take the flags themselves (the common genetic mutations) and inject them back into the patient in small amounts to get the body's own defences fighting against the cancer."

NOT A CURE - YET

Prof Swanton is adamant "this is not a cure, though we hope it might have the potential to improve outcomes", and, his peers hope, offer a totally new way of treating cancer.

"It gives us vital clues about how to specifically tailor treatment for a patient using their own immune system," says Prof Peter Johnson, Cancer Research UK's lead clinician, "as well as filling in gaps in our knowledge and giving us hope of developing better treatments for cancers we have previously found hardest to treat."

CANCER CURE: A TIMELINE

1923 Radiotherapy first used to treat cervical cancer

1954 Proof of a link between smoking and lung cancer first published

1956 First chemotherapy drug used to treat a rare tumour

1963 Discovery of first human cancer virus

1972 Drug for testicular cancer developed

1994-95 The first breast cancer genes BRAC-1 and BRAC-2 discovered.

2011 International Cancer Genome Consortium formed to map the genetic faults behind 50 types of cancer

2013 Trial finds taking the drug anastrozole daily can halve the risk of breast cancer in older women

2016 Scientists build nanoparticles that act as "Trojan horse" vessels to ferry chemotherapy drugs direct to cancers


 
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