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New drug combination shows promise for resistant leukaemia

Patients with acute myeloid leukaemia (AML) can look forward to the development of new therapies, say researchers

Date:
May 18, 2016
Source:
Walter and Eliza Hall Institute
Summary:
Patients with acute myeloid leukaemia (AML) can look forward to the development of new therapies following the discovery of a new way to kill cells that are dangerously multiplying. A process known as apoptosis (programmed cell death) - which is a natural and necessary response to keep the proliferation of human cells in check - is interrupted in cancers, including AML, leading to unchecked cell growth.
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Professor Paul Ekert, Ms Chunyan Ma, Professor John Silke, and Dr Gabriela Brumatti have discovered a new way to kill cancer cells.
Credit: The Walter and Eliza Hall Institute of Medical Research

Patients with acute myeloid leukemia (AML) can look forward to the development of new therapies following the discovery by Walter and Eliza Hall Institute researchers of a new way to kill cells that are dangerously multiplying.

A process known as apoptosis (programmed cell death) -- which is a natural and necessary response to keep the proliferation of human cells in check -- is interrupted in cancers, including AML, leading to unchecked cell growth.

Institute researcher Dr Gabriela Brumatti and her PhD student Chunyan Ma are part of a team, led by Professor John Silke from the Institute and Professor Paul Ekert from the Murdoch Childrens Research Institute in Melbourne, investigating ways to target particular types of AML, hoping to increase the chance of a cure for the patient while limiting damage to healthy cells.

Dr Brumatti said traditional chemotherapies, which induce apoptosis, had a high relapse rate. For example, within five years of completing treatment 50 per cent of AML patients suffer a relapse of their cancer. Of those who relapse, only 50 per cent survive.

Her team tried a 'blue sky' approach to their research and inhibited apoptosis of AML cells in order to unleash an alternative form of cell death called necroptosis. They found this necroptosis cell death pathway was more effective at killing AML than apoptosis. These findings have just been published in the research journal, Science Translational Medicine.

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

"It has been speculated that inducing necroptosis might be an effective way to kill cancer cells," said Professor Silke. "Our work now demonstrates clearly it is a clinically feasible and safe approach."

Dr Brumatti said since cancer cells often acquire resistance to traditional chemotherapy-induced apoptosis, this novel type of chemotherapy had the potential to be used to treat otherwise impossible to treat leukemias.


Story Source:

Materials provided by Walter and Eliza Hall Institute. Note: Content may be edited for style and length.


Journal Reference:

  1. G. Brumatti, C. Ma, N. Lalaoui, N.-Y. Nguyen, M. Navarro, M. C. Tanzer, J. Richmond, M. Ghisi, J. M. Salmon, N. Silke, G. Pomilio, S. P. Glaser, E. de Valle, R. Gugasyan, M. A. Gurthridge, S. M. Condon, R. W. Johnstone, R. Lock, G. Salvesen, A. Wei, D. L. Vaux, P. G. Ekert, J. Silke. The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia. Science Translational Medicine, 2016; 8 (339): 339ra69 DOI: 10.1126/scitranslmed.aad3099

Cite This Page:

Walter and Eliza Hall Institute. "New drug combination shows promise for resistant leukaemia: Patients with acute myeloid leukaemia (AML) can look forward to the development of new therapies, say researchers." ScienceDaily. ScienceDaily, 18 May 2016. <www.sciencedaily.com/releases/2016/05/160518152819.htm>.
Walter and Eliza Hall Institute. (2016, May 18). New drug combination shows promise for resistant leukaemia: Patients with acute myeloid leukaemia (AML) can look forward to the development of new therapies, say researchers. ScienceDaily. Retrieved May 28, 2017 from www.sciencedaily.com/releases/2016/05/160518152819.htm
Walter and Eliza Hall Institute. "New drug combination shows promise for resistant leukaemia: Patients with acute myeloid leukaemia (AML) can look forward to the development of new therapies, say researchers." ScienceDaily. www.sciencedaily.com/releases/2016/05/160518152819.htm (accessed May 28, 2017).

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