Blood cancers

‘Blue-sky’ approach to AML shows promise


A ‘blue sky’ project undertaken by researchers at the Walter and Eliza Hall Institute may have found a key to the treatment of acute myeloid leukaemia (AML) that has eluded researchers around the globe for decades.

The researchers, who published their findings in Science Translational Medicine believe using a new pathway to destroy the disease may prove more effective in patients with AML who have either relapsed or are resistant to existing chemotherapy.

Institute researcher Dr Gabriela Brumatti told the limbic that the research had the potential to significantly improve AML survival rates, which are currently around 27%.

She said traditional chemotherapies, which induce apoptosis had a high relapse rate, but had not changed in about 30 years.

“Within five years of completing treatment 50% of AML patients suffer a relapse of their cancer. Of those who relapse, only 50% survive,” she said.

She said her team had adopted a ‘blue sky’ approach to their research and inhibited apoptosis of AML cells rather than induced it, in order to unleash an alternative form of cell death called necroptosis – and this pathway proved more effective at killing AML than apoptosis.

In preclinical trials they used a combination of drugs, including the new anti-cancer drug birinapant, and emricasan, a US Food and Drug Administration (FDA) approved inhibitor of apoptosis.

Dr Brumatti’s institute colleague, Professor John Silke, who is also part of the research team, said it had been speculated that inducing necroptosis might be an effective way to kill cancer cells.

“Our work now demonstrates clearly it is a clinically feasible and safe approach,” he said.

Dr Brumatti told the limbic that it had made sense to look at an alternative to the pathway existing chemotherapies had been using for some 40 years.

“So far all therapy targets one cell pathway, the same cell pathway,” she said. “This study shows that moving aside of this pathway, we can get results. We hope it could vastly improve survival rates.”

However, she said she did not see this as a replacement for existing therapies.

“It is more for patients who have become resistant to traditional chemotherapy-induced apoptosis, more for patients who are relapsing, not a replacement for existing therapy,” she said.

In any case, she said it could be 20 years before treatment is available as a mainline treatment, provided it gets through the relevant clinical trials and approval processes.

“That might not sound so attractive but if you don’t start somewhere you will never know,” she said. “It’s all about patient safety, so we need to make sure the therapy works and is safe.”

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