Using new drugs to block instructions from a cancer-promoting gene

This project aims to develop and test a new class of drug that targets a known cancer-promoting gene in a completely new way. Although at an early stage, this could pave the way for clinical trials of a new drug that might be effective against as many as 50 per cent of advanced prostate cancers.

We’ve known for several years that a cancer-promoting gene called ERG is inappropriately switched on in over 50 per cent of prostate cancers, and is especially active in advanced disease. However, it’s very difficult to develop drugs against the protein encoded by the ERG gene, so instead this research team wants to block its activity a step before the protein gets made.

They’ll do this by developing a drug that disrupts the ‘splicing’ of the ‘messenger RNA’ produced by the ERG gene. (Messenger RNA is the gene’s instructions to make the ERG protein; it needs to be ‘spliced’ i.e. assembled together before it can do this).

This class of drug – called splice switching oligos, or SSOs - are relatively new and the technology to be able to deliver them to patients is ongoing development. Other SSOs are currently being tested in other diseases, so the precedent for taking them through to clinical trials has been set but this is the first time we’ve seen a proposal to try using them to treat prostate cancer.

In the first year of this project, the team will work with collaborators in New York to develop a range of SSOs that they believe will disrupt ERG activity. They will test these drugs rigorously in prostate cancer cell lines to determine which SSOs work best.

In the second year, they will move these tests into animal models of prostate cancer in collaboration with the University of Bristol to determine how well the drugs can slow or prevent prostate cancer growth in whole-body contexts.

Overall, this project aims to carry out the essential pre-clinical testing that will demonstrate whether or not there is value in taking this new type of drug through to clinical trials for advanced prostate cancer. This type of treatment has never been attempted before but, if it is successful, it could eventually produce a new way to treat prostate cancer in up to 50 per cent of men diagnosed with advanced disease.

Grant information

Reference - RIA15-ST2-030
Researcher - 
Professor Michael Ladomery
Institution - University of the West of England
Award - £136,390