Is DNA damage repair leading to cancer?

Prof Ken Mills, Queen's University Belfast and Leuka Project Grant 2018

Ken Mills Leuka Research Project

What is this research looking at?

The DNA within our cells holds the code, in the form of genes, for ensuring that our cells grow and work efficiently and effectively. Any damage to the DNA code might affect the correct function of the cells, particularly damage to genes that regulate cell growth and development, which if unrepaired can lead to cancer. Fortunately, the cell has a system that detects DNA damage and activates a repair mechanism if it is minor and can be fixed or, if the damage is to severe, the detection process activates cell death, a process called apoptosis. As people get older the rate of ineffective DNA damage repair increases, which can often lead to the development of cancer.  

A type of blood cancer called myelodysplastic syndrome (MDS) occurs in some elderly patients and some of these can then develop a more aggressive type of blood cancer called acute myeloid leukaemia (AML). MDS and then AML often arise as the blood cells accumulate DNA damage, some of which will affect the way that DNA is structured or the way that RNA, made from DNA, is spliced before being made into proteins.  

Our previous studies have shown that some mutations also have an impact on the way that DNA is repaired after damage, leaving the cells with limited means for repairing damaged DNA.  In this scenario, we hope to block the cancer cells remaining DNA repair pathways, using novel less toxic drugs, thereby triggering a catastrophic build-up of damaged DNA in these cells, resulting in cancer cell death. This is particularly important in elderly patients whom are more likely to develop MDS and AML, as they often can’t tolerate traditional chemotherapies, which are relatively toxic.  

The funded project will combine laboratory and computer-based studies to determine how we use deficiencies in DNA repair as a therapy. Our investigation will identify candidate therapies to slow or halt the progression of MDS particularly towards AML as both diseases have an unmet need for new treatments.

What could this mean for leukaemia patients? 

Better therapies that attack the weakness in the leukaemia cells caused by the defective DNA repair, leading to improved outcomes for patients. 

Leuka funding has enabled me to undertake valuable research into AML which has an unmet need for new and effective therapies.

Professor Ken Mills, Queen's University Belfast