Protein “handbrake” stops leukemia
Melbourne researchers found a protein that can stop leukemia from spreading.
Hhex is a protein that helps leukemia cells to grow uncontrollably. Targeting the said protein can treat acute myeloid leukemia (AML) by stopping cells growth and division.
Existing AML treatments are not cancer-specific and can kill healthy cells. The treatments also have serious side-effects. About three quarters of patients relapse after only a short period of treatment, with a five-year survival rate of just 24 per cent.
“There is an urgent need for new therapies to treat AML,” said Dr McCormack. “We showed blocking the Hhex protein could put the brakes on leukemia growth and completely eliminate AML in preclinical models. This could be targeted by new drugs to treat AML in humans.”
“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. “Hhex works by recruiting epigenetic factors to growth control genes, effectively silencing them. This allows the leukemia cells to reproduce and accumulate more damage, contributing to the speed of AML progression,” Dr Shields said.
Dr McCormack said drugs that inhibit epigenetic modification had been previously used to treat AML, but caused significant toxicity because their targets were also required for normal blood cell function.
“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.”
Category: Features, Technology & Devices
