{Reference Type}: Journal Article
{Title}: Sotorasib for Vascular Malformations Associated with KRAS G12C Mutation.
{Author}: Fraissenon A;Bayard C;Morin G;Benichi S;Hoguin C;Protic S;Zerbib L;Ladraa S;Firpion M;Blauwblomme T;Naggara O;Duruisseaux M;Delous M;Boitel C;Bringuier PP;Payen L;Legendre C;Kaltenbach S;Balducci E;Villarese P;Asnafi V;Bisdorff A;Guibaud L;Canaud G;
{Journal}: N Engl J Med
{Volume}: 391
{Issue}: 4
{Year}: 2024 Jul 25
{Factor}: 176.079
{DOI}: 10.1056/NEJMoa2309160
{Abstract}: KRAS gain-of-function mutations are frequently observed in sporadic arteriovenous malformations. The mechanisms underlying the progression of such KRAS-driven malformations are still incompletely understood, and no treatments for the condition are approved. Here, we show the effectiveness of sotorasib, a specific KRAS G12C inhibitor, in reducing the volume of vascular malformations and improving survival in two mouse models carrying a mosaic Kras G12C mutation. We then administered sotorasib to two adult patients with severe KRAS G12C-related arteriovenous malformations. Both patients had rapid reductions in symptoms and arteriovenous malformation size. Targeting KRAS G12C appears to be a promising therapeutic approach for patients with KRAS G12C-related vascular malformations. (Funded by the European Research Council and others.).