Working in Partnership

PROTACing medulloblastoma: turning existing chemistry upside down to design a new therapeutic approach

This project, in partnership with Kidscan, aims to develop a better understanding of medulloblastoma, the most common type of malignant brain tumour in children, which can also occur in adults.

Outcomes for medulloblastoma have improved over the years but there are currently no effective treatments other than highly toxic radiotherapy and chemotherapy that often lead to severe and lifelong impairments.

There is a great need to develop a better understanding of the disease and to develop new treatments that directly target the tumour
specifically whilst avoiding damage to the body’s normal tissues. The team will focus on a protein that is often mutated in this form of cancer, having identified a chemical compound which will bind to this protein.

Without modification, this compound could be detrimental to the patient and so the team will work with an industry partner to add components onto the chemical in order to lead to the proteins destruction and removal from the cell.

The project seeks to understand how the chemical binds to its target protein and whether it can be further optimised through chemical
engineering. The researchers believe that the results of the project will open up new treatments for medulloblastoma that can feed into industrybased drug development programmes.

In a second strand of the project, the team hopes to demonstrate that the same molecule can be reconfigured as a chemical building block for drugs relevant to multiple cancer types and could have the potential to open up new treatment in medulloblastoma and other childhood cancers.