法国马拉德斯儿童医院Guillaume Canaud团队研究了索托拉西布治疗KRAS G12C突变相关血管畸形的疗效。相关论文于2024年7月17日发表在《新英格兰医学杂志》上。

KRAS功能获得性突变在散发性动静脉畸形中经常被观察到。这种KRAS驱动的畸形进展的机制尚不完全清楚，也没有获批的任何治疗方法。

研究组展示了特异性KRAS G12C抑制剂索托拉西布在减少血管畸形体积和提高携带嵌合KRAS G12C突变的两种小鼠模型存活率方面的有效性。然后，他们给两名患有严重KRAS G12C相关动静脉畸形的成年患者服用了索托拉西布。两名患者的症状和动静脉畸形大小都迅速减轻。靶向KRAS G12C似乎是治疗KRAS G12C-相关血管畸形患者的一种有前景的治疗方法。

附：英文原文

Title: Sotorasib for Vascular Malformations Associated with KRAS G12C Mutation

Author: Antoine Fraissenon, Charles Bayard, Gabriel Morin, Sandro Benichi, Clément Hoguin, Sanela Protic, Lola Zerbib, Sophia Ladraa, Marina Firpion, Thomas Blauwblomme, Olivier Naggara, Michael Duruisseaux, Marion Delous, Clothilde Boitel, Pierre-Paul Bringuier, Léa Payen, Christophe Legendre, Sophie Kaltenbach, Estelle Balducci, Patrick Villarese, Vahid Asnafi, Annouk Bisdorff, Laurent Guibaud, Guillaume Canaud

Issue&Volume: 2024-07-17

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.

DOI: NJ202407170000001

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2309160