This article reframes drug discovery around a central strategic question: not simply ‘Can we inhibit this target?’ but ‘What’s the optimal way to modulate this biology for the right patient?’ Through a case study on dabrafenib’s paradoxical MAPK activation, it shows why conventional inhibition can fail and how next-generation BRAF inhibitors and targeted protein degraders avoid those pitfalls.

It then zooms out to map the full range of modern modalities, from antibodies and RNA therapeutics to ADCs, PROTACs, molecular glues, and tri-complex inhibitors, and the frameworks that guide their selection based on biology, mechanism, and practical constraints. With examples like Revolution Medicines’ macrocyclic molecular-glue approach to RAS, the piece positions modality choice as a competitive advantage in creating the next generation of precision medicines.