Attività anticancro dell'inibizione di RAS-GTP nel cholangiocarcinoma.

About 25% of cholangiocarcinoma (CCA) tumors harbor KRAS mutations. Here, we investigated the activity of RAS(ON) multi-selective inhibitors, which target the active, GTP-bound state of mutant and wild-type variants of canonical RAS isoforms, in preclinical models and in patients with KRAS mutant CCA. RAS(ON) multi-selective inhibitors yield strong anticancer responses in cell- and patient-derived xenografts and immunocompetent allograft models. Consistent with these preclinical findings, we describe clinical activity of the RAS(ON) multi-selective inhibitor daraxonrasib in two patients with advanced KRAS G12 CCA. RAS-GTP inhibition also potentiates the activity of current standard-of-care C