Researchers from the Walter and Eliza Hall Institute in Melbourne, Australia, have shown they can stop leukemia in its tracks by targeting a protein that puts the handbrake on cancer cell growth. The researchers discovered that targeting a protein called Hhex could cure acute myeloid leukemia (AML) in preclinical disease models, and could be a key target for new therapies for human leukemia. Credit: Walter and Eliza Hall Institute
Melbourne researchers have showed that they can stop leukemia in its tracks by targeting a protein that puts the handbrake on cancer cell growth.They discovered targeting protein Hhex could cure acute myeloid leukemia (AML) in preclinical disease models, and could be a key target for new therapies for human leukemia. Dr Ben Shields and Dr Matt McCormack from the Walter and Eliza Hall Institute discovered that loss of the Hhex protein put the handbrake on leukemia cell growth and division. The protein is a critical factor enabling AML cells to grow uncontrollably, a hallmark of cancer.
AML is an aggressive blood cancer that appears suddenly, grows quickly and has a poor prognosis. Existing treatments for AML are associated with serious side-effects. About 3/4 of patients relapse after only a short period of treatment, with a 5yr survival rate of just 24%. Hhex was a particularly attractive therapeutic target as it was overproduced in leukemia and, while essential for leukemia cell growth, was not needed by healthy blood cells. “Most existing treatments for AML are not cancer cell-specific, and unfortunately kill off healthy cells in the process,” Dr McCormack said.
“Hhex is only essential for the leukaemic cells, meaning we could target and treat leukemia without toxic effects on normal cells, avoiding many of the serious side-effects that come with standard cancer treatments. We also know that most people with AML have increased levels of Hhex, often associated with adverse outcomes, further indicating it is an important target for new AML drugs.”
Dr Shields said AML cells switched off the controls that strictly manage cell growth and division. “Every cell has control genes that are activated when a cell is stressed, such as in the early stages of cancer, and stop the damaged cell from reproducing.” Dr Shields said. While these control genes are still present in AML cells, they are switched off through a process called epigenetic modification. This allows the leukemia cells to reproduce and accumulate more damage.
“Unlike the epigenetic factors targeted previously, Hhex only regulates a small number of genes and is dispensable for normal blood cells. This gives us a rare opportunity to kill AML cells without causing many side effects,” said Dr McCormack. “We now hope to identify the critical regions of the Hhex protein that enable it to function, which will allow us to design much-needed new drugs to treat AML.” http://www.wehi.edu.au/news/protein-handbrake-halts-leukaemia-its-tracks
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