Small-Molecule Inhibitors and Degraders Targeting KRAS-Driven Cancers

Drug resistance continues to be a major problem associated with cancer treatment. One of the primary causes of anticancer drug resistance is the frequently mutated RAS gene. In particular, considerable efforts have been made to treat KRAS-induced cancers by directly and indirectly controlling the activity of KRAS. However, the RAS protein is still one of the most prominent targets for drugs in cancer treatment. Recently, novel targeted protein degradation (TPD) strategies, such as proteolysis-targeting chimeras, have been developed to render undruggable targets druggable and overcome drug resistance and mutation problems. In this study, we discuss small-molecule inhibitors, TPD-based small-molecule chemicals for targeting RAS pathway proteins, and their potential applications for treating KRAS-mutant cancers. Novel TPD strategies are expected to serve as promising therapeutic methods for treating tumor patients with KRAS mutations.

Automated summary

The study explores methods for treating cancers caused by KRAS mutations, including controlling the activity of RAS pathway proteins, small-molecule inhibitors, and targeted protein degradation strategies. These novel approaches are expected to provide promising therapeutic options for tumor patients with KRAS mutations.