Optimising radiosensitivity of uveal melanoma by targeting DNA damage response

Brief lay background

Uveal melanoma (UM) is the most common cancer of the eye in adults, with around 500 cases in the UK per year. Although it can be sight and life-threatening in 50% of patients, the treatment for UM involves radiotherapy which generally works well.

This project makes use of the Clatterbridge Cancer Centre which contains the only proton beam therapy centre in the UK that is dedicated to treatment of eye cancers.

What problem/knowledge gap does it help address

Some UM are radiation resistant leading to ineffective treatment and tumour recurrence, and larger tumours are still treated with eye removal (enucleation) due to significant side-effects related to larger radiation doses. Researchers are looking to understand how radiotherapy treatments for UM can be optimised, and lead to the minimising of side-effects of the radiation to the rest of the eye. This will lead to preserving more vision of UM patients.

Aim of the research project

To investigate how cancer responds to x-ray therapy proton beam therapy. This will identify drug strategies that can optimise radiotherapy treament in promoting UM cell killing.

Key procedures/objectives

1. Provide the radiosensitivity profile of UM cells to investigate the efficiency of DNA damage repair and cell death.
2. Optimise the radiosensitivity of UM cells, by inhibiting DNA damage repair.

Potential impact on people with sight loss

There are significant opportunities for development of more effective treatment strategies for UM to improve vision outcomes in patients receiving radiotherapy.

Optimisation of the radiosensitivity of UM cells would allow for lower radiation doses to be applied in clinical treatment, which in turn would reduce damage to normal surrounding tissue. This project uses 3D models which more accurately represent the structure and associated environment of the original tumour, as well as how this mimics the response to radiation and drug treatment. New potential therapeutic avenues looking at inhibition of DNA repair will be further explored.