Melbourne researchers have shown they can stop leukaemia 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 leukaemia (AML) in preclinical disease models, and could be a key target for new therapies for human leukaemia.
Dr Ben Shields and Dr Matt McCormack from the Walter and Eliza Hall Institute’s Cancer and Haematology division discovered that loss of the Hhex protein put the handbrake on leukaemia 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 three quarters of patients relapse after only a short period of treatment, with a five-year survival rate of just 24 per cent.
Dr McCormack said discovering how AML overcame normal cellular controls on growth and division was a breakthrough in the search for new therapies.
“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 leukaemia growth and completely eliminate AML in preclinical models. This could be targeted by new drugs to treat AML in humans.”
He said Hhex was a particularly attractive therapeutic target because it was overproduced in leukaemia and, while essential for leukaemia 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 leukaemia 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 leukaemia 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.”
The Latest on: Leukaemia
via Google News
The Latest on: Leukaemia
- Blood cancer symptoms: Five of the most commonly ignored signs of acute leukaemiaon September 15, 2019 at 6:48 am
Blood cancer is one of the most common cancers in the UK, with one in 16 men and one in 22 women developing the disease in their lifetime. There are several different types of blood cancer, however ...
- Leukaemia Careon September 14, 2019 at 3:55 pm
Kate Stallard, who was very ill with leukaemia, makes the Radio 4 Appeal on behalf of the charity Leukaemia Care. Show more Kate Stallard, who was very ill with leukaemia, makes the Radio 4 Appeal on ...
- Acute lymphoblastic leukaemia explainedon September 14, 2019 at 9:05 am
As Selby teenager Francesca Taylor-Draper opens up about her battle with blood cancer and its impact on her life, we take a look at the illness. Acute lymphoblastic leukaemia is the most common form ...
- Heart-rending photo shows girl 5, comforting her little brother, 4, while he’s sick from chemo during leukaemia battleon September 9, 2019 at 4:19 am
THIS heartbreaking photo shows a little girl rubbing her four-year-old brother's back while he's sick from chemo during his cancer battle. Beckett Burge was diagnosed with acute lymphoblastic ...
- Heartbreaking moment girl, 5, takes care of little brother with leukaemiaon September 9, 2019 at 3:49 am
Older sister Aubrey wants to help her brother back to recovery after he was diagnosed in April 2018 (Picture: Kennedy News and Media) A mum has released heartbreaking pictures of her four-year-old ...
- Boy, 4, with leukaemia comforted by his sister, 5, in mum's heartbreaking photoon September 9, 2019 at 2:28 am
Aubrey Burge rubs her cancer-stricken brother Beckett's back and reassures him as he leans over the toilet being sick ...
- Couple both battled leukaemia after suffering back pain and red marks on fingerson September 8, 2019 at 2:30 am
Mark and Jan Hurley, who live in St Ives, Cornwall, were diagnosed with leukaemia, a cancer which starts in blood-forming tissue, some years apart ...
- ‘Incurable’ leukaemia patients are declared ‘cancer FREE thanks to new treatment’on September 3, 2019 at 1:09 am
A GROUNDBREAKING new treatment for leukaemia has left patients cancer free, medics have revealed. Fourteen people with 'incurable' acute lymphoblastic leukaemia (ALL) were left with no trace of the ...
- ‘Very promising results’ in trial of new leukaemia treatmenton September 2, 2019 at 8:10 am
A trial of a new form of treatment for leukaemia has shown “very promising results”, according to Great Ormond Street Hospital. Researchers have tested a faster-acting version of an existing treatment ...
- Patients with incurable leukaemia declared cancer-free after groundbreaking treatmenton September 2, 2019 at 8:04 am
A new treatment for an incurable form of leukaemia has been hailed by experts after it left patients without a trace of the disease. The patients were treated with a faster acting version of CAR-T ...
via Bing News