This comment hits the nail on the head. Another big consideration with the technology in this paper that hasn't been mentioned in this thread is that it opens up a huge range of possibilities for targeting "undruggable" protein targets. Most drugs are small molecules that bind to sites an (relatively much larger) proteins, thereby getting in the way of their function. Unfortunately the vast majority of proteins do not have a site that can be bound by a molecule in a way that 1) has high affinity, 2) has high specificity (doesn't bind to other proteins) and 3) actually abolishes the protein's activity.

With "induced proximity" approaches like the one in this study, all you need is a molecule that binds the target protein somewhere. This idea has been validated extensively in the field of "targeted protein degradation", where a target protein and an E3 ubiquitin ligase, a protein that recruits the cell's native proteolysis machinery, are recruited to each other. The target protein doesn't have to be inactivated by the therapeutic molecule because the proteolysis machinery destroys it, so requirement #3 from above is effectively removed.

The molecule in this study does something similar to targeted protein degradation, but this time using a protein that effects gene expression instead of one that recruits proteolysis machinery. The article focuses on the fact that cancers are addicted to BCL6. This is an important innovation in the study and an active area of research (another example at [1]), but leaves out the fact that these induced proximity platforms are much more generalizable than traditional small molecules because it's the proteins that they recruit that do all the work rather than the molecules themselves. This study goes a long way to validate this principle, pioneered by targeted protein degradation and PROTACs, and shows that it can be applied broadly.

[1] https://www.biorxiv.org/content/10.1101/2024.07.27.605429v1