Exploiting synthetic lethality for the treatment of glioma

High-grade gliomas are complex and devastating tumours, for which despite multiple modes of treatment, including surgery, chemotherapy and radiation therapy, survival times remain very short, on average of ~14 months. Nrf2 is a protein that allows adaptation to stress conditions, which are experienced by cancer cells due to sub-optimal levels of oxygen and nutrients in their environment. Hsp90 is a chaperone for multiple proteins, ensuring their correct folding, stability and function. Hps90 is particularly crucial for cancer cells as they have proteins with mutations, which render them unstable without the chaperone activity of Hsp90. Thus, Hsp90 inhibitors are being developed for cancer treatment. Cancer cells often hijack and activate both Nrf2 and Hsp90. One consequence of Nrf2 activation is an increase in the levels of an enzyme called NQO1, which converts a class of Hsp90 inhibitors (known as pro-drugs) to much more potent compounds (actual drugs). This project will test the hypothesis that such pro-drugs, combined with Nrf2/NQO1 activation, will cause death of glioma cells, and stop glioma growth. Because Hsp90 inhibitors have been in clinical trials and one of the most potent Nrf2 activators recently entered clinical practice, the findings from this project may lead to a clinical trial in glioma patients.

This PhD opportunity is for UK students only.

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Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education.