The molecular landscape of PDAC is driven largely by prevalent KRAS mutations.6 Efforts to develop KRAS inhibitors have failed because of the high affinity of RAS proteins for the pocket binding site for GTP.7 Novel KRAS G12C inhibitors are under development.8 However, KRAS G12D, the most common RAS mutation in PDAC, remains undruggable. Targeting KRAS in PDAC by using downstream MAP kinase inhibitors, such as MEK inhibitors, has been unsuccessful.9,10 Targeting ERK downstream of KRAS has emerged as a promising strategy in models in vivo.
gicasym.org daily news