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Life-changing discovery made possible with donor support

01 June 2021
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Introduction

Thanks to the generosity of donors, WEHI researchers have made a critical discovery that could benefit people with the aggressive blood cancer acute myeloid leukemia.

Dr Gabriela Brumatti and her team investigated whether SMAC-mimetics, a new class of anti-cancer agents, could be made more potent by combining them with other drugs. The team discovered inhibitors of the MDR1 drug pump had the potential to enhance the effectiveness of SMAC-mimetics as a treatment for acute myeloid leukemia (AML).

MDR1 is a protein found in healthy cells but can become elevated in some cancers. The protein pumps certain molecules out of cells. In healthy cells, it protects against the accumulation of unwanted substances, but in cancer cells MDR1 can pump anti-cancer drugs out of the cell, preventing them from working effectively and making the cancer resistant to therapy.

Dr Brumatti said inhibitors of MDR1 were able to stop the pump, helping the drugs stay in the cell and exert their anti-cancer effects.

“When we combined MDR1 inhibitors and SMAC-mimetics, we saw that the AML cells retained the SMAC-mimetics and started to die,” she said.

“We think MDR1 inhibitors could potentially be combined with SMAC-mimetics to create an effective new combination treatment.”
Dr Gabriela Brumatti

Dr Brumatti said the combination of MDR1 inhibitors and SMAC-mimetics could also kill leukaemia ‘stem cells’, which are thought to be a source of cancer recurrence.

“This discovery is important, because it suggests the drug combination could provide long-term benefits for patients,” she said.

Dr Brumatti said community support was critical for this research.

“We were thrilled that more than 400 people supported this research, providing more than $80,000 for the project. It also provided encouragement for the research team – it was wonderful to know that so many people believed in us.”

Thank you to all the generous supporters who helped make this medical research breakthrough possible.

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