New cancer ‘inhibitor’ could lead to improved treatment options

Researchers have discovered a potential advancement in the treatment of chronic myeloid leukaemia (CML), which they hope will one day offer an improved option for treating patients with this form of blood cancer.

The study– published in Science Translational Medicine and led by the University of Glasgow in collaboration with LifeArc – has discovered a potential ‘autophagy inhibitor’ which, when used in combination with current cancer therapies, could lead to better treatment options for CML cancer patients.

Autophagy is a cellular process that is frequently induced in cancer cells as a survival mechanism against anticancer treatments such as chemotherapy, radiotherapy and targeted drugs. Therefore, inhibiting this process, in conjunction with standard treatment, has been proposed as a potential combination therapy for individuals with cancer. However, current approved autophagy inhibitors lack potency and have demonstrated limited efficacy in clinical trials.

In collaboration with LifeArc, a UK based charity, the University of Glasgow scientists validated a preclinical autophagy inhibitor – called MRT403 – which, when used in combination with current CML therapies, reduced the growth of cancer cells derived from individuals with CML, and in leukaemia mouse models. It’s the first inhibitor of its kind to show efficacy against leukaemia cells and the scientists hope it may also be applicable for other cancer types, such as pancreatic, colorectal and lung cancers.

At present, CML patients are treated with tyrosine kinase inhibitors, otherwise known as TKIs, which have transformed the clinical management of the disease. Treatment of patients with TKIs alone rarely cures the disease, but they can hold its advancement at bay. As a result, most patients need to remain on TKIs for the rest of their lives, with associated side effects and the risk of developing resistance to the drugs.

Dr Vignir Helgason, head author of the study from the University of Glasgow, said: “We have been investigating the process of autophagy in leukaemia cells for several years. Therefore, we are very excited about our new findings, and to be collaborating with a pharmaceutical company to further develop this approach for CML. There is also evidence that this approach may be applicable to other cancer types that use autophagy as an escape mechanism to survive anticancer treatment, which is currently being tested in a clinical trial for advanced tumours.”

The paper, ‘ULK1 inhibition promotes oxidative stress–induced differentiation and sensitizes leukemic stem cells to targeted therapy,’ is published in Science Translational Medicine. The study is funded by Tenovus Scotland, Leukaemia UK, The Kay Kendall Leukemia Fund, Blood Cancer UK, Cancer Research UK, Friends of Paul O’Gorman Leukaemia Research Centre and The Howat Foundation.





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