Blood cancer breakthrough could lead to ‘new era’ of treatment, say leading scientists

By Staff 6 Min Read

A study has discovered that blocking an enzyme in the body’s cells which senses changes in oxygen levels could stop the disease from progressing to a more serious stage

A drug breakthrough could usher in a “new era” for how an aggressive form of blood cancer is treated, scientists have said.

Described by researchers as a “largely incurable disease”, acute myeloid leukaemia (AML) is a cancer which causes the bone marrow to produce a large number of abnormal blood cells. A study has discovered that blocking an enzyme in the body’s cells which senses changes in oxygen levels could stop the disease from progressing.

In the presence of oxygen, these enzymes known as hypoxia-inducible factor prolyl hydroxylases (PHDs) become active to target and destroy proteins called hypoxia-inducible factor (HIF). When oxygen levels are low, PHD enzymes are less active, leading to higher HIF levels.

The study, co-led by the Institute of Cancer Research, London, and the University of Oxford, explored if boosting HIF levels could prevent the progression of AML. They genetically modified mice and de-activated PHD enzymes, which increased HIF levels and stopped disease progression without impacting the production of normal blood cells.

A similar enzyme-blocking process is used in drugs that treat anaemia, according to researchers, and showed the same effect on leukaemia in mouse cells and patient samples. The research team has also created a new compound called IOX5, which inhibits PHDs without impacting other enzymes.

Kamil Kranc, a professor of haemato-oncology at The Institute of Cancer Research, London, said: “Therapy for acute myeloid leukaemia has barely changed in several decades. There is a huge need to discover better treatments for this aggressive disease.

“We’ve shown for the first time that targeting the pathways that our cells use to respond to oxygen levels could provide a new way to treat leukaemia, without impacting the normal production of blood cells within the bone marrow.” AML is most common in patients over the age of 75. According to the NHS, there are about 3,100 people diagnosed with the disease each year in the UK.

It is hoped the findings of the research which was funded by Cancer Research UK, Medical Research Council and Barts Charity, and published in Nature Cancer will now be tested in clinical trials. Prof Kranc added: “Our next challenge is to progress the existing drugs and our new, more selective compound, to clinical trials.

“We’re hopeful this research will pave the way towards a new era of AML treatments, and we’d like to explore whether these therapies could also be beneficial for solid tumours.” Professor Kristian Helin, chief executive of The Institute of Cancer Research, London, said: “Cancer exists in a complex ecosystem within the body.

“This work provides important insights into that ecosystem, and the way in which cancer uses signals within the environment such as those relating to oxygen levels to grow and develop. This study is also an excellent example of cancer researchers and chemists working closely together to develop and test new cancer therapeutics.

“It’s exciting to see how a concept develops through a fundamental discovery project and the development of a first-in-class small molecule inhibitor, to potentially benefiting patients with this devastating type of cancer, and I look forward to seeing this research progress into clinical trials.”

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