Mainly by the use of genomics technology, single-cell gene expression analysis, and thorough CRISpen screens, significant advances in cancer biology over the past ten years have revolutionised medication development. Many therapeutic targets these developments found were first judged "undruggable" because of sizeable protein-protein interaction surfaces devoid of clear ligand-binding pockets. Still, the scientific community has embraced creating strategies to target these challenging proteins. Among the notable achievements are creating medicines aimed at KRASG12C, covalent bonding techniques to take advantage of latent binding sites, and PROTAC technology-which uses the ubiquitin-proteasome system to break down target proteins. These days, new trends in drug development centre on creative lead-finding tools and fresh drug modalities. For typically "undruggable" proteins, proximity-based platforms, including chemoproteomic techniques, have evolved as valuable tools for locating covalent ligands and possible binding sites. Furthermore, the idea of proximity induction-as shown by IMiDs and PROTACs-has created fresh paths for inducing protein breakdown and thereby targeting less ligandable proteins. Targeting RNA also presents fresh opportunities for challenging-to-treat cancer targets since it seems a complementary approach to protein targeting. These developments are transforming the field of drug discovery and broadening the range of druggable targets when combined with attempts to overcome drug resistance with fresh drugs and combination therapies.