It’s a good time to take stock of an early but important niche where the basic concept is the¬†hijacking of the natural ubiquitin-proteasome (waste disposal) system for protein degradation therapeutics.

Traditional targeted therapies involve a small molecule or an antibody (in monoclonal or bispecific format) to inhibit an oncogenic target thereby shutting down the activity of the tumour, at least for a while.

Getting to the centre of things

What if we could find a way to biologically destroy oncogenic proteins instead – especially those which are hard to reach in normal circumstances such as protein-protein interactions?

The inherent potential for this concept would extend what we could do in terms of the proteome, but can it be done in people?

We have, after all, seen the selective estrogen receptor degraders (SERDs) evolve with one drug approved and several companies developing third generation versions in early stage clinical trials, so why not other targets too?

The simple truth of the matter is this elegant idea – while simple in theory – is technically quite challenging involving quite different obstacles from what we have seen with TKIs and antibodies.

Nevertheless, the difficulty has not fazed companies from trying and in looking at the broad landscape, we found 24 companies actively involved in protein degradation research in a multitude of targets and cancers. These span publicly traded biotechs, privately held companies, and of course, big Pharma.

Who are they and what can we learn from them in order to anticipate some of the issues to be addressed?

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