Scientists from the Institute of Cancer Research (ICR), the University of Oxford and Queen Mary University of London have revealed a promising new treatment strategy for an aggressive form of blood cancer, acute myeloid leukaemia (AML).
The study, published in Nature Cancer, was funded by Cancer Research UK, the Medical Research Council and Barts Charity.
Responsible for more than 3,000 new cases every year in the UK, AML is an aggressive form of leukaemia that increases the production of immature white blood cells, damaging the bone marrow and other organs in the body.
Currently, the majority of AML patients receive chemotherapy and bone marrow transplants to control their condition. However, these treatments are not always effective and can cause toxic side effects.
Researchers aimed to understand whether enzymes known as hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs) could offer a potential drug target for treating AML.
PHD enzymes are active in the presence of oxygen and target HIF proteins for their destruction. When oxygen levels are low, PHD enzymes are less active and result in increased levels of HIF.
In studies of mice, researchers showed that blocking or genetically activating PHDs to inactivate enzymes increased HIF levels and stopped leukaemia from forming or progressing without disturbing the normal production of blood cells.
Similarly, using mouse cells and patient samples, researchers revealed the same effect when inactivating PHD using existing drugs currently used to treat anaemia.
The team generated a new first-in-class PHD inhibitor called IOX5, which works to selectively inhibit PHDs without inactivating other enzymes.
IOX5 was found to significantly block AML progression and further increase the anti-cancer effect when used in combination with AbbVie and Roche’s leukaemia treatment, Venclexta/Venclyxto (venetoclax), which is currently approved in the EU and US to treat newly diagnosed AML.
“Our next challenge is to progress the existing drugs and our new, more selective compound to clinical trials,” said Professor Kamil Kranc, professor of haemato-oncology, ICR.
Kranc continued: “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.”