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.).
摘要：
在散发性动静脉畸形中经常观察到KRAS功能获得突变。这种KRAS驱动的畸形发展的潜在机制仍未完全理解，并且没有批准这种情况的治疗方法。这里,我们展示了索托拉西的有效性，一种特定的KRASG12C抑制剂，在两个携带镶嵌KrasG12C突变的小鼠模型中减少血管畸形的体积并提高存活率。然后，我们对两名患有严重KRASG12C相关动静脉畸形的成年患者进行了索托拉钠治疗。两名患者的症状和动静脉畸形大小均迅速减轻。针对KRASG12C似乎是KRASG12C相关血管畸形患者的一种有希望的治疗方法。（由欧洲研究理事会和其他机构资助。).
