South Australian scientists have made a significant advance in overcoming drug resistance among patients with acute myeloid leukemia, a rare blood cancer that kills now sufferers within a few years.
Researchers from the University of South Australia and SA Pathology’s Center for Cancer Biology have discovered a way to suppress a specific protein that promotes resistance to drugs commonly used to treat AML patients.
One of the lead authors, Stuart Pitson, said the finding could revolutionize the treatment of AML, a disease that recently claimed the lives of SA football great Russell Ebert and professional golfer Jarrod Lyle.
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“Each year in Australia, around 900 people are diagnosed with AML, a cancer of the blood and bone marrow characterized by an overproduction of cancerous white blood cells called leukemic blasts,” Professor Pitson said.
“These cells crowd out normal white blood cells, which then can’t do their usual infection-fighting work, thereby increasing the risk of infections, low oxygen levels and bleeding.”
SA Rathology hematologist David Ross received many AML patients initially responded to Venetoclax, a new therapy recently listed on the PBS, but over time AML cells became resistant.
Using a large biobank of patient-donated AML biopsies and world-leading advanced pre-clinical models, the researchers demonstrated that by regulating lipid metabolism in the body, a protein called Mcl-1, a protein that facilitates drug resistance, was inhibited in AML cells.
“This process makes AML cells exquisitely sensitive to Venetoclax while leaving the normal white blood cells unaffected,” SA Pathology researcher Jason Powell said.
The team is now working to optimize drugs targeting this pathway to take into clinical trials for AML patients.
Prof Ross said for most people with AML, the chances of long-term survival were no better now than they were last century.
“Now, we have a chance to remedy that,” he said.
“New treatments that prevent Venetoclax resistance have the potential to prolong survival, or even increase the chances of a cure in a disease for which improved outcomes are desperately needed.”
The SA research has been published in the hematology journal Blood.