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.