Son of Sevenless homolog 1 mRNA (SOS1 mRNA) (SOS1 mRNA)

Son of Sevenless homolog 1 (SOS1) mRNA is the messenger RNA transcript that encodes the SOS1 protein, a critical guanine nucleotide exchange factor (GEF) for RAS family GTPases (NCBI Gene ID: 6654). SOS1 plays a pivotal role in the MAPK/ERK signaling pathway by facilitating the exchange of GDP for GTP on RAS proteins, thereby transitioning them from an inactive to an active state (UniProt: P35555). In many malignancies, particularly those driven by KRAS mutations, SOS1 acts as a key node that maintains RAS signaling and facilitates resistance to targeted therapies. Targeting the SOS1 mRNA via RNA interference (RNAi) or antisense oligonucleotides (ASOs) aims to reduce the total cellular concentration of the SOS1 protein, providing a broader inhibitory effect on RAS activation compared to inhibitors that only target specific RAS mutants (PubMed: 30104351). While small molecule inhibitors targeting the SOS1 protein (e.g., BI-1701963) are currently in clinical trials, mRNA-directed strategies are being explored in preclinical research as a means to achieve potent and specific knockdown of the RAS-MAPK signaling axis (PubMed: 31811050). This approach is intended to overcome compensatory signaling mechanisms that often lead to resistance against direct KRAS G12C inhibitors.

Other names

SOS1 transcriptSon of Sevenless 1 mRNASOS-1 mRNASon of Sevenless homolog 1 transcript

RNA interference (RNAi) or antisense-mediated degradation of mRNA to prevent translation of the SOS1 protein (PubMed: 30104351).