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Direct Targeting KRAS Mutation in Non-Small Cell Lung Cancer: Focus on Resistance - PubMed

Direct Targeting KRAS Mutation in Non-Small Cell Lung Cancer: Focus on Resistance - PubMed

Source : https://pubmed.ncbi.nlm.nih.gov/35267628/

KRAS is the most frequently mutated oncogene in non-small cell lung cancers (NSCLC), with a frequency of around 30%, and encoding a GTPAse that cycles between active form (GTP-bound) to inactive form (GDP-bound). The KRAS mutations favor the active form with inhibition of GTPAse activity. ...


Conclusion/Relevance: Small molecules such as sotorasib are now the first targeted drugs for KRAS G12C mutation, preventing conversion of the mutant protein to GTP-bound active state. Little is known about primary or acquired resistance. Acquired resistance does occur and may be due to genetic alterations in the nucleotide exchange function or adaptative mechanisms in either downstream pathways or in newly expressed KRAS G12C mutation.