Two-pronged treatment for blood cancer

A research team led by the Walter and Eliza Hall Institute has found that treatment of acute myeloid leukaemia (AML) — the most deadly form of blood cancer — may be improved by combining two recently developed drugs. The discovery has been published in the journal Cancer Cell.

AML causes around 850 deaths in Australia each year — more than any other type of blood cancer. Many people with AML respond poorly to treatment, with less than one-third surviving for five years after their diagnosis. High-dose chemotherapy, the current treatment for people with AML, has many toxic side effects.

The researchers had been searching for ways to enhance the anticancer effects of birinapant — a smac-mimetic (SM) developed by US biotech company TetraLogic Pharmaceuticals currently in clinical trials. Dr Najoua Lalaoui said the team discovered that the combination of birinapant with p38 inhibitors — which have also been in clinical trials for cancer treatment — had a much stronger anticancer effect than either agent alone.

“Our findings have made us hopeful that a combination of birinapant and a p38 inhibitor may be more effective in treating AML than current therapies, and also have less toxicity for patients,” she said. “We tested forms of AML that are highly resistant to chemotherapy and found that birinapant and p38 inhibitors could even kill these cancer cells, which is great news.”

Professor John Silke said the discovery was underpinned by two decades of research at the institute into inhibitor of apoptosis (IAP) proteins, which are targeted by birinapant.

“We have had a long-term interest in how IAPs function in healthy and diseased cells,” he said. “Our research into how IAPs work made an important contribution to the initial development of birinapant as a specific IAP inhibitor.

“Our latest research is part of an exciting next step, fine-tuning how birinapant can be used in the clinic to enhance its anticancer effects.”

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