Kirsten rat sarcoma viral oncogene homolog mutant messenger RNA (KRAS mutant mRNA)

KRAS mutant mRNA refers to messenger RNAs transcribed from mutated alleles of the KRAS gene, an oncogene encoding a small GTPase involved in regulating cell division and signal transduction. Activating mutations (e.g., G12C, G12D, G12V) in the KRAS gene lead to constitutively active KRAS protein, resulting in persistent activation of downstream pathways such as RAF-MEK-ERK and PI3K-AKT-mTOR, driving uncontrolled cellular proliferation, survival, and malignant transformation. KRAS mutations are especially prevalent in pancreatic, colorectal, and lung cancers, making these mutant transcripts crucial diagnostic and therapeutic biomarkers. Drugs targeting the mutant KRAS protein are in clinical use, while direct RNA-targeted therapies are in development. Therapeutic challenges include drug resistance, the biochemical diversity of KRAS mutations, and the difficulty in selectively targeting mRNA without impacting wild-type KRAS function.

Other names

KRAS mutant transcriptKRAS mutant messenger RNAmutant KRAS mRNAmutant KRAS transcript

Therapeutic strategies targeting KRAS mutant mRNA primarily involve RNA interference (siRNA/ASO-mediated degradation of mutant KRAS mRNA, preventing mutant protein expression). Indirectly, drugs like sotorasib and adagrasib exert their effect via covalent inhibition of the mutant KRAS protein, which is the downstream product of the KRAS mutant mRNA.