Synergistic Co-Targeting Of MYC And KRAS In Lung Cancer By Novel Ligand-Directed Inverted Chimeric RNAi Molecules

Nearly a quarter of non-small cell lung cancer cases (NSCLC) are driven by activating mutations in the GTPase KRAS, which has traditionally been a challenging therapeutic target. However, recent identification of a stable binding pocket in the KRASG12C variant has led to the rapid development of mutant-specific small-molecule inhibitors. However, these show only modest clinical responses and result in acquired resistance. There is an urgent need to identify novel therapies that can overcome this resistance and also target non-KRASG12C mutations.