Solving the problem of unacceptable toxicity in treatment

It’s about individualising treatment, not refusing it

The list of defined, unacceptable toxicities offers researchers a guide to further work around figuring out methods of identifying which patients are genetically predisposed to such side-effects.

“The next step is looking for those side effects in patients and then looking at their genetics to do an investigation in pharmacogenetics, which is all about the association between a gene, a drug and a side-effect,” Dr Conyers says.

The goal of pharmacogenetics is to make medications safer for the individual, so they avoid significant and potentially life-long side effects from taking medications.

Another challenge for clinicians and researchers is to demonstrate that toxicity can be avoided through the fine-tuning of therapies without affecting survival rates. In fact, this is already the case for some medications, particularly in the treatment of leukemia.

Where to next?

The next practical steps involve collaboration on a large scale, Dr Conyers says.

“Unacceptable toxicities happen in about five per cent of the patients we see,” she says. “Whenever you’re looking at trying to associate a gene with a toxicity, you need large numbers of patients to do that. So collaboration is key.”

There is already a major international effort in pharmacogenetics to collaborate, to pool resources and expertise in order to supercharge research efforts. That’s important, because the process of identifying particular genetic associations and figuring out the actions that can and should be taken around that association is a long one.

Find out more: UPDATE Behind the science: Dr Rachel Conyers.

Then, clinically, what we need is a stepwise process around how we introduce acting on those genes in the clinic,” Dr Conyers says. “What we need to prove is that if we do alter drug doses, or we change drugs, there’s no decrease in a patients survival.”

 Until recently, pharmacogenetics has not been that easy to get funded!

Now however, the individualisation of treatment at a genetic level is becoming a reality across various therapies. A greater understanding of its value is beginning to develop.

 “For years, people have asked why I’m concentrating on drug side effects,” she says. “Curing cancer is really sexy, people have told me, so why don’t I do that?”

“But in the last two to three years, particularly in childhood leukemia where the survival rates are now pushing 90 per cent, there has been a pivot in the focus towards trying to avoid toxicities. And pharmacogenetics more broadly across Australia is growing. There’s definitely been a shift, and with that has come collaboration. The future is very exciting.”