For Professor Tim Hughes, progress in cancer research isn't just measured by big headlines and column inches – it's about the patients he has been treating for years and their quality of life.
A haematologist based in Adelaide, Professor Hughes has spent more than two decades focused on chronic myeloid leukaemia (CML), a blood cancer that has been completely transformed during that time.
"When I started, it was almost always fatal," he says. "Most patients survived just three to four years. Then around 2000, we began to see the emergence of targeted therapies, and that completely changed the outlook for patients."
The arrival of these therapies – tyrosine kinase inhibitors – meant there were drugs that could target the exact fault causing the cancer. In CML, a genetic mutation sends blood cells into overdrive. These drugs essentially switch that signal off, stopping the cancer in its tracks. Professor Hughes and his team were among the first to trial them.
"The results were dramatic," he says. "It was a completely different way of treating cancer – targeting the specific driver of the disease rather than using more general treatments."
Since then, his work has helped fuel three major breakthroughs. The first was developing a game-changing, highly sensitive blood test that can detect tiny traces of the disease. "It means we can track exactly how well a patient is responding," he explains. "This is a very important step in the treatment process, which provides us with a clearer picture."
The second – and perhaps most exciting – breakthrough was the discovery that some patients could stop treatment altogether. "We used to say to patients, this is the drug that's going to keep you alive, but you'll be on it for the rest of your life," he explains. "But we started to see patients with such low levels of leukaemia that we couldn't detect it anymore. And what we found was that some patients could stop therapy and remain completely free of detectable leukaemia. At the moment, only about a third of patients achieve treatment-free remission, so we've still got a long way to go."
The third major breakthrough from Tim Hughes's CML work was the development and early use of a highly specific next-generation drug that works differently from earlier treatments. In simple terms, this is a new kind of targeted therapy that is much more precise than earlier drugs. It blocks the cancer-driving protein in a different way and avoids affecting many of the normal enzymes in the body.
"It is so specific in its ability to inhibit the leukaemia kinase that it doesn't affect other normal kinases at all," he says. "It's the first time that's ever been achieved. We've now treated over 200 patients in Australia with this drug as first-line therapy. And the results have been extremely good."
With around five to 10 per cent of patients still developing aggressive disease, the next step, Professor Hughes believes, lies in combining better drugs with new approaches – particularly harnessing the immune system. He and his colleagues are increasingly interested in how immune responses might help maintain deep remissions and reduce the likelihood of relapse over time.
This work is driven by a large multidisciplinary team at SAHMRI, alongside collaborators at the Royal Adelaide Hospital and Adelaide University, with strong integration between laboratory research and clinical care.
But Professor Hughes is quick to point out another key group – his patients. "Almost everyone is willing to take part in clinical trials," he says. "Even if it won't help them directly, they want to help the next person. That's pretty remarkable."
For Professor Hughes and his team, that sense of purpose is what continues to drive the work forward and sustain its momentum. "You can see the difference this work makes," he says. "That's what matters – to have patients who generally don't even know they are being treated is a huge step forward."
