Main
sarcoma
PROLIFERATION, VIRUS, SARCOMA, SOLID TUMORS
The Kirsten rat sarcoma virus oncogene homologue (KRAS) protein is a guanosine triphosphatase (GTPase) that cycles between the active GTP-bound and inactive GDP-bound states to regulate cell proliferation, migration and survivalDivarasib (GDC-6036) is an orally bioavailable, covalent KRAS G12C inhibitor that turns off its oncogenic signaling by irreversibly locking the protein in an inactive state. In vitro studies have also shown that divarasib is 5 to 20 times as potent and up to 50 times as selective as compared to the KRAS G12C inhibitors sotorasib and adagrasibDespite the encouraging antitumor activity with single-agent divarasib in patients with CRC, adaptive feedback reactivation of RAS–MAPK signaling, a proposed key mechanism of resistance to KRAS G12C inhibition in CRC, occurs frequently and ultimately limits efficacyDivarasib in combination with other anticancer therapies is currently being evaluated in an ongoing phase 1b study in patients with advanced or metastatic solid tumors harboring a 