Personalised treatment is the key to fewer side effects and longer survival rates when it comes to treating cancer, writes CLAIRE O'CONNELL
THERE WAS a time when people spoke of looking for “the” cure for cancer, as if it were a singular thing. But we now know that often the most effective chemotherapy approaches are not one-size-fits-all.
Instead, they can involve profiling the person’s cancer at a molecular level and then etching the tumour’s name on the bullet with “personalised” drug regimes.
The move towards getting up close and more personal about cancer treatment goes back to the 1970s when it became apparent that some cancers responded better to treatments than others, according to Dr Seamus O’Reilly, a consultant oncologist at Cork’s Mercy and South Infirmary Victoria Hospitals.
“There were enormous advances in leukaemia and testicular cancer treatment, yet for patients with advanced disease like lung or bowel cancer, we seemed to have met a brick wall in that they didn’t respond as well to treatment,” he says.
“Then came a focus on why this was happening – why weren’t our treatments more effective, why weren’t we able to get better results?
“That led to genetic studies that showed cancer was complex, and there were multiple genetic changes in cancer which prevented them from responding to treatment.”
On the face of it, those tricky genetic changes and the range of differences between individual cancers sound like they should be bad news for finding treatments to tackle the disease.
But, in practice, studies have been able to identify molecular signatures of individual tumours and custom-design treatments to attack them more directly. The upshot is hopefully fewer side effects and longer survival for the patient.
A poster-child for the personalised approach is herceptin, a “smart” drug to target and block the growth of breast tumours that overexpress a gene called her-2.
An international trial (which involved patients at Irish centres) showed that if you profile tumours to find the 25 per cent that come up as her-2 positive and use herceptin when treating them, the results for those patients are likely to be markedly better.
“I was at the meeting where the results of that study were presented and the significant reduction in relapse rate of the patients was phenomenal,” recalls O’Reilly.
“Also the other thing that impressed was that in these patients when their cancer spread, it had traditionally been very difficult to treat, but now we found that when we treated them, if you added herceptin to chemotherapy the success rate was much greater.”
Working out the molecular kinks of tumours has even opened up new ways to treat challenging conditions such as gastrointestinal stromal tumours (Gist), which previously had poor success rates with standard chemotherapy, according to O’Reilly.
Research identified that an enzyme called C-kit wasn’t functioning properly in Gist tumours, and a drug called Glivec – which is also used as a treatment for chronic myeloid leukaemia – could address the problem.
“That has had a significant impact,” says O’Reilly. “There are few side effects and you can continue it long term.”
Another important “biomarker” is the K-ras gene in colorectal cancer.
Mutations in the K-ras gene can signal when a patient won’t respond well to particular chemotherapy agents. If identified, it means patients may be spared the side effects of a treatment regime that is not likely to be effective, explains O’Reilly.
“We couldn’t identify this in the past, but now by prospectively identifying it, you can prevent people getting treatment that won’t benefit them,” he says.
At present, samples from Cork are sent to England to be tested for K-ras mutations, and O’Reilly believes it would make sense for Ireland to have a centralised lab for this kind of testing.
“We have a lot of medical schools and university hospitals, and it may be that resources should be pooled, that in a time of financial constraint we should have a reference molecular pathology lab,” he says, noting that personalised cancer treatments are continuing to develop.
“More and more of these drugs are going to be coming down the line, and testing will refine who will and won’t benefit from treatment,”according to O’Reilly.
