Targeting vulnerabilities in genetically defined tumour cells

End of project summary

Main Messages 

Increases in our understanding of the biology of cancer need to be translated into better treatments for the disease. At a fundamental level, cancer is caused by damage to genes, leading to changes in cell behaviour. If we can characterise the genetic changes in an individual’s cancer then we can use that information to target the cancer with specific drugs, making their treatment much more personalised and precise. 

To do that we need to develop more therapies that are targeted to a specific genetic alteration. We also need a way to accurately characterise the cancer’s genetic makeup. As that changes with time, we ideally need a way to sample the genetic make-up at multiple time points during patients’ treatment. 

Some of the genes that are involved in cancer are also linked to inherited tumour predisposition syndromes. The TSC1/2 genes are linked to the condition tuberous sclerosis, which is characterised by the growth of tumour in multiple organs, seizures and intellectual disability. . 

In collaboration with Professor Andy Tee from Cardiff University, we have identified a novel target, Ref-1/APE1, that is implicated in the pathology of tuberous sclerosis and cancer. We have shown that inhibiting Ref-1/APE1 in TSC1/2 deficient cells normalises aspects of cell behaviour and reduces growth of tumour models. 

I have been awarded a Health and Research Wales Health Research Grant to investigate where we can use artificial intelligence techniques to better understand the clinical significance of ctDNA. This is genetic material, which has been shed from a cancer cell into the bloodstream. As the ctDNA can be extracted from a blood sample, it may be a means to monitor a cancer’s genetic changes during treatment. 

I have also developed the infrastructure to undertake genomic research and implement findings into practice across Wales and published papers in areas such as precision oncology, breast cancer and inherited tumour predisposition syndromes.