Deadly blood cancer may be best treated with two-pronged approach
Researchers from the Walter and Eliza Hall Institute (Victoria, Australia) have discovered that the best treatment for the most deadly form of blood cancer may be to combine two recently developed drugs.
A team from the Walter and Eliza Hall Institute (Victoria, Australia) have found that a combination of recently developed drugs show promise in pre-clinical studied as a novel treatment for acute myeloid leukemia (AML). The drugs, birinapant and p38 inhibitors, have both been studied as cancer therapies, offering hope that combining the two could be safely administered to AML patients, who have few alternative treatment options.
The researchers, led by Najoua Lalaoui and John Silke, made the discovery while researching ways to enhance birinapant’s anti-cancer effects. Lalaoui described her team’s excitement to discover that the combination had a much stronger anti-cancer effect than either agent administered alone. "Both p38 inhibitors and birinapant have been safely used in humans in clinical trials," Lalaoui explained. "We are hopeful that the combination of these agents could be an effective anti-cancer treatment."
AML is the cause of around 850 deaths annually in Australia alone, more than any other type of blood cancer, and many patients respond poorly to treatment, with fewer than one-third surviving for five years after diagnosis. The current treatment for AML, high-dose chemotherapy, has many toxic side-effects.
"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," Lalaoui described. "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."
Silke added that the team has spent two decades researching proteins called IAPs, which are targeted by birinapant. "We have had a long term interest in how IAPs function in healthy and diseased cells," he stated. "Our research into how IAPs work made an important contribution to the initial development of birinapant as a specific IAP inhibitor.”
Silke continued: “Birinapant has been used in clinical trials for several types of cancers. Our latest research is part of an exciting next step, fine tuning how birinapant can be used in the clinic to enhance its anti-cancer effects.”
Lalaoui N, Hänggi K, Brumatti B et al. Targeting p38 or MK2 Enhances the Anti-Leukemic Activity of Smac-Mimetics. Cancer Cell 29 (2), 145-158 doi:10.1016/j.ccell.2016.01.006 (2016); http://www.wehi.edu.au/news/two-pronged-attack-increases-potency-new-anti-cancer-drugs