Kirsten rat sarcoma virus proto-oncogene, GTPase mRNA (KRAS mRNA)

Kirsten rat sarcoma virus proto-oncogene (KRAS) wild-type mRNA is the transcript responsible for the synthesis of the KRAS protein, a small GTPase that functions as a critical mediator in cellular signal transduction. The KRAS protein operates as a molecular switch, cycling between active GTP-bound and inactive GDP-bound states to regulate downstream pathways such as the MAPK/ERK and PI3K/AKT cascades, which are essential for cell growth, proliferation, and survival (NCBI Gene ID: 3845; UniProt: P01116). While KRAS mutations are hallmark drivers in various malignancies, including pancreatic, colorectal, and lung cancers, the wild-type mRNA is increasingly viewed as a therapeutic target through the use of RNA-targeting modalities like antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) (PubMed: 33067318). These therapies aim to silence KRAS expression by inducing the degradation of the mRNA transcript or inhibiting its translation, thereby suppressing the oncogenic signaling driven by both mutant and wild-type forms in a "pan-KRAS" approach. However, because wild-type KRAS is vital for normal physiological processes, a major therapeutic challenge involves minimizing on-target toxicity in healthy tissues while effectively reducing the protein burden in tumor cells (PubMed: 31548606). Current research focuses on optimizing delivery systems and identifying therapeutic windows to safely exploit KRAS mRNA as a target in oncology.

Other names

KRASK-RasK-Ras 2Kirsten rat sarcoma viral oncogene homolog mRNAc-K-ras mRNAKRAS1KRAS2RASK2KI-RASC-K-RASK-RAS2AK-RAS2B

Antisense-mediated mRNA degradation (RNase H-dependent) or RNA interference (RNAi) leading to reduced KRAS protein expression.