Projects we fund

Overview

Acute myeloid leukaemia (AML) is an aggressive disease that is responsible for roughly 40% of deaths from blood cancer in children every year. Although modern medicine has made dramatic advances in the treatment of this disease, further improvements cannot be achieved by increasing the intensity of current therapies due to the unacceptable toxicities this would entail. For this reason, research has focused on trying to block the action of different cancer genes that are responsible for this disease. However, it is known that many different cancer genes can cause AML and so a therapy that blocks the action of any one of these will only be useful in a proportion of cases. Another approach is to find cellular pathways that may be hijacked in common by the different cancer genes. Therapies designed to block these could then be used across a broad range of different AML patients. Professor Owen Williams, his team and others have shown that one such pathway does exist. It is controlled by a molecule called MYB and laboratory research has shown that blocking this pathway results in the death of blood cancer cells from different types of AML. The next step is to find safe and effective drugs that can block this pathway in children suffering from AML.

Professor Williams and his team plan to establish a new treatment for children suffering from AML, based on their recent research. This project aims to produce data that will be sufficient to initiate a phase I clinical trial for this devastating disease. The team plan to investigate in more detail the cellular mechanisms hijacked in this type of cancer and find ways in which these can be blocked. The overall goal is to develop a new and safe treatment for AML in children.

The team have recently published research showing that the drug mebendazole, which is used in millions of children worldwide to treat parasitic worm infections, kills AML cells by blocking the action of MYB. They are currently working out how mebendazole can be used in the clinic by testing which of the current AML treatments it can be used together with. This project is based on further research that undertaken looking at ways in which AML cells can resist mebendazole. This work found two pathways that can be safely controlled to increase the killing of AML cells by mebendazole. Professor Williams and his team propose testing these modified treatments in a broad range of blood cancer cells from different types of AML. They also plan to continue their work at finding new ways in which to improve the effectiveness of mebendazole in treating AML in children. Since there are many laboratories and companies that are developing new treatments that block the action of MYB, the team also plan to use a laboratory model to find cellular pathways in AML cells that affect their ability to grow and survive when MYB is blocked.

What difference will this project make?

This research is crucial to the rapid translation of mebendazole into the clinic for children suffering from AML but also to any new therapy that emerges in the near future designed to block MYB in AML. This project aims to produce sufficient evidence to support the start of a Phase I clinical trial for mebendazole, in combination with other treatments, in children suffering from AML. If this is successful, it will make an impact on the treatment of these children, potentially improving their treatment outcomes without increasing the toxicities they are exposed to.