zotatifin + sotorasib

**Zotatifin + sotorasib** is a combination therapy under investigation for cancers harboring the KRAS G12C mutation. Sotorasib is a targeted, covalent, and irreversible inhibitor of KRAS G12C, binding to a unique cysteine residue in KRAS and locking it in its inactive GDP-bound state, thereby shutting down downstream oncogenic MAPK signaling and promoting anti-tumor activity[2][6]. Zotatifin is a selective inhibitor of eukaryotic initiation factor 4A (eIF4A), a helicase central to initiating mRNA translation, especially for oncogenic drivers and cell growth factors. By combining zotatifin (which blocks translation of cancer-related mRNAs) with sotorasib (which shuts down KRAS G12C-driven signaling), the regimen aims for synergistic suppression of tumor growth, enhanced cell cycle arrest, and potentiation of pro-apoptotic responses. This combination may be under clinical investigation for advanced solid tumors, particularly non-small cell lung cancer and colorectal cancer harboring KRAS G12C mutations.

Other names

zotatifinLumakrassotorasib