To review therapeutic strategies targeting KRAS mutations in non-small cell lung cancer (NSCLC) and propose a classification schema for novel KRAS-targeting molecules.
Approach:
Review of KRAS-targeting strategies: The article discusses the development of covalent KRAS G12C inhibitors and other novel KRAS-targeting molecules, including pan-KRAS and pan-RAS inhibitors.
Classification schema: A classification schema for KRAS-targeting molecules is proposed, focusing on their chemical strategies and potential combinations with existing therapies.
Key Findings:
Oncogenic KRAS mutations are present in up to 30% of NSCLC patients.
Covalent KRAS G12C inhibitors received FDA accelerated approval in 2021.
Multiple novel KRAS-targeting molecules are in clinical testing, including those targeting non-G12C alleles.
Interpretation:
Limitations:
The review captures a snapshot of a rapidly evolving field, which may become outdated quickly.
The organization of the review attempts to balance clinical and chemical perspectives, which may lead to complexity.
