chronic myeloid leukaemia (CML) is currently treated with a class of drugs called Tyrosine Kinase Inhibitors and in the majority of cases this treatment is successful, with around 90% of patients recovering from the disease. However in the majority of patients a subset of cancer cells – CML stem cells – are resistant to Tyrosine Kinase Inhibitors.
Professor Tessa Holyoake from the University of Glasgow’s team discovered that CML stem cells avoid the impact of Tyrosine Kinase Inhibitor treatments by going into a state called autophagy in response to the drug. This means that they begin to shut down and use nutrients from within the cell to survive in what is effectively suspended animation. In this state the drug cannot kill them and so later they can initiate a resurgence of the disease. Hydroxychloroquine has been shown to kill cells that are undergoing autophagy and the trial is designed to test whether this is a potential route for treatment in patients.
Although hydroxychloroquine probably isn’t the final answer for treating resistant CML stem cells, we are aware that there is interest from the pharmaceuticals industry in developing new drugs that target cells undergoing autophagy. We are therefore very hopeful that once we can prove that in principle this approach works, it could lead relatively quickly to a new treatment for patients for whom Tyrosine Kinase Inhibitors don’t provide a full cure
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