Targeting stress response proteins to selectively kill Neurofibromatosis type 1 tumours

Summary

There is a clear need to discover new drugs to target NF1-deficient tumour cells. This project will test whether inhibition of the cellular stress response pathways causes selective death of NF1-deficient cells.

How are we doing it?

• Viability assays will identify targets (siRNA knockdowns) that selectively decrease NF1-mutant cell viability in a panel of human NF1-deficient cell lines.
• The top targets will be identified, and small molecule compounds that target them will be tested in a panel of human NF1-deficient cell lines.
• A range of concentrations will be tested. We will select those that have no impact on healthy cells yet selectively kill NF1-deficient cells.

What happens next?

By the end of this project, this work will provide preliminary data for an MRC grant application to perform pre-clinical testing of the identified compounds using mouse models of NF1. This will then lead to clinical trials in the future.

Funding

NIHR Exeter BRC Small Project Grant.

People Involved

Dr Megan Stevens, Prof Ben Housden.