KRAS-Degrading Compounds: A Novel Approach to Treat Cancer by Targeting Both Wild-Type and Mutated KRAS Forms.

KRAS, a critical gene involved in cellular processes, can initiate tumor formation when mutated. These mutations occur in about 20-30% of all human cancers, linking KRAS particularly to lung, colorectal, and pancreatic cancers. Its "undruggable" reputation, owing to the difficulty in inhibiting its activity, is being challenged by promising developments. Notably, covalent inhibitors such as sotorasib show success in binding to specific KRAS mutations. Also, PROTACs, an emerging technology, effectively reduce protein levels in the cell, inspiring similar strategies using KRAS-degrading compounds. Novel combination therapies have demonstrated improved anti-tumor effects. This Patent Highlight reveals exemplary KRAS-degrading compounds with anti-tumor activity, effective against both wild-type and mutated KRAS. They present desirable pharmacological properties, promising a revolution in cancer treatment upon further clinical investigation.