WEHI team delivers a ‘Muhammad Ali’ blow to acute myeloid leukaemia

A discovery that delivers a double blow to blood cancer cells, offering new hope for acute myeloid leukaemia patients, has been hailed the Muhammad Ali of treatments.

It is being called the Muhammad Ali for blood cancer treatment because it delivers a knockout blow with one drug followed by another that “stings” cancer cells like a bee.

Researchers at WEHI in Melbourne are using the boxing great as an analogy to explain their discovery, which they say offers hope for people with acute myeloid leukaemia (AML), one of the most common types of blood cancers.

For the first time the team has tested a dual combination of drugs, one that is already a standard anti-cancer treatment for AML and the second an emerging immunotherapy drug that activates a protein called STING.

The results of the “promising” early research were published in the journal Cancer Cell and next will be clinical trials run by WEHI scientists with Victorian patients.

Study co-first author Dr Sarah Diepstraten said the team had examined cancer samples from patients with AML and treated them in the lab with the killer combination.

“It’s really impressive – combining (the drug) venetoclax with this emerging immunotherapy treatment (activating STING) can actually eradicate AML,” Dr Diepstraten said.

“It offers hope for patients rather than a cure.”

Dr Sarah Diepstraten, Dr Eddie La Marca, Associate Professor Gemma Kelly and Dr Yin Yuan at the WEHI institute. Picture: WEHI

She said this was important as some AML was particularly aggressive and resistant to treatment and there was a critical need for better therapies.

“This is the one-two punch combo that could be the knockout blow for AML. You could almost paraphrase the famous boxer Muhammad Ali and say this treatment floats like a butterfly and stings like a bee.”

Dr Diepstraten said the research set out to find out why some patients with AML did not respond as well to venetoclax.

“What we found was some patients who have mutations in a protein called P53, which is a tumour suppressor, do not respond as well,” she said.

“We found that if we activate this protein called STING, we can actually compensate for that loss of P53 to kill cancer cells.”

WEHI said the P53 protein protects cancer cells forming, but when it became defective it could significantly increase the risk of cancer developing.

One of the country’s leading medical research institutes, WEHI, said while STING-activating drugs had been investigated to fight solid tumours by activating the body’s immune response, this was the first time they had been used to directly target mechanisms within the cancer cells, stimulating the natural processes that cause these cells to die.

Dr Diepstraten said the team presented the results at a conference recently and clinicians said they had never seen such strong laboratory results for AML.

Scientists at the WEHI will start preparing to do clinical trials with Victorian patients.

In a statement Associate Professor Gemma Kelly, co-senior author and a laboratory head in WEHI’s Blood Cells and Blood Cancer division, said venetoclax and drugs that activate STING played complementary roles in killing cancer at the cellular level.

“It is these two drugs, working in tandem that led to the highly effective killing of AML cancer cells in our lab-based tests, in results that were truly striking,” she said.

“Within a cancer cell, venetoclax blocks the machinery of the cell that is keeping it alive. In certain blood cancers where this response is sub-optimal, STING agonists can supercharge this effect to deliver cancer a deathly blow.”

Dr Diepstraten said as someone who does the more basic research, she would love to think her research will help people.

“But to see it progress so quickly into a clinical trial will be really exciting and rewarding.”