The KRAS-G12C inhibitor: activity and resistance.
Jiao LiuRui KangDaolin TangPublished in: Cancer gene therapy (2021)
Although it has long been deemed "undruggable", with the development of drugs specifically binding the KRAS-G12C mutant protein, clinical trials that directly inhibit oncogenic RAS have recently made promising improvements. In particular, the covalent KRAS-G12C inhibitors sotorasib and adagrasib are used to treat patients with advanced non-small cell lung cancer (NSCLC) carrying KRAS-G12C mutations. Unfortunately, the vast majority of patients do not respond to KRAS-G12C inhibitor therapy, mainly due to intrinsic or acquired resistance caused by cellular, molecular, and genetic mechanisms. Improving the understanding of drug response in the tumor microenvironment may continue to promote the design, testing, and clinical application of KRAS-G12C inhibitors.
Keyphrases
- wild type
- advanced non small cell lung cancer
- clinical trial
- small cell lung cancer
- epidermal growth factor receptor
- end stage renal disease
- ejection fraction
- newly diagnosed
- gene expression
- emergency department
- prognostic factors
- stem cells
- transcription factor
- binding protein
- patient reported outcomes
- mesenchymal stem cells
- single molecule
- study protocol
- replacement therapy