索托拉西布治疗与 G12C 突变相关的血管畸形。
Sotorasib for Vascular Malformations Associated with G12C Mutation.
机构信息
From Service d'Imagerie Pédiatrique, Hôpital Femme-Mère-Enfant, Hospices Civils de Lyon, Bron (A.F., L.G.), CREATIS Unité Mixte de Recherche 5220, Villeurbanne (A.F.), INSERM Unité 1151, Institut Necker-Enfants Malades (A.F., C. Bayard, G.M., S.B., C.H., S.P., L.Z., S.L., M.F., V.A., L.G., G.C.), Université Paris Cité (C. Bayard, G.M., S.B., C.H., S.P., L.Z., S.L., M.F., T.B., O.N., C.L., E.B., V.A., L.G., G.C.), Unité de Médecine Translationnelle et Thérapies Ciblées (C. Bayard, G.M., C.H., S.P., L.Z., S.L., M.F., L.G., G.C.), Service de Neurochirurgie Pédiatrique (S.B., T.B.), Service de Néphrologie et Transplantation Adultes (C.L.), and Laboratoire d'Oncohématologie (S.K., E.B., P.V., V.A.), Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Département de Neuroradiologie, Hôpital Lariboisière, AP-HP (A.B.), and Service de Neuroradiologie Interventionnelle, Hôpital Sainte Anne, AP-HP (O.N.), Paris, Service de Radiologie Mère-Enfant, Hôpital Nord, Saint Etienne (A.F.), the Respiratory Department and Early phase EPSILYON Est, Louis Pradel Hospital, Oncopharmacology Laboratory, Cancer Research Center of Lyon, Unité Mixte de Recherche INSERM 1052, Center National de la Recherche Scientifique (CNRS) 5286 (M. Duruisseaux), Centre de Recherche en Neurosciences de Lyon, INSERM Unité 1028, CNRS Unité Mixte de Recherche 5292 (M. Delous, C. Boitel), and the Institute of Pharmaceutical and Biological Sciences (L.P.), Université Claude Bernard Lyon 1, and Service d'Anatomie Pathologique, Hôpital Edouard Herriot, Hospices Civils de Lyon (P.-P.B.), Lyon, the Circulating Cancer Program, Cancer Institute (L.P.), and Laboratoire de Biologie Médicale Multi Sites du Centre Hospitalier Universitaire de Lyon, Service de Biochimie et Biologie Moléculaire (L.P.), Hospices Civils de Lyon, and the Center for Innovation in Cancerology of Lyon, EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Université Claude Bernard Lyon 1 (L.P.), Oullins-Pierre-Bénite - all in France.
出版信息
N Engl J Med. 2024 Jul 25;391(4):334-342. doi: 10.1056/NEJMoa2309160. Epub 2024 Jul 17.
gain-of-function mutations are frequently observed in sporadic arteriovenous malformations. The mechanisms underlying the progression of such -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 G12C mutation. We then administered sotorasib to two adult patients with severe 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 G12C-related vascular malformations. (Funded by the European Research Council and others.).
功能获得性突变在散发性动静脉畸形中经常观察到。导致这种畸形进展的机制仍不完全清楚，也没有批准用于该病症的治疗方法。在这里，我们展示了 sotorasib（一种特定的 KRAS G12C 抑制剂）在减少血管畸形体积和改善携带镶嵌 G12C 突变的两种小鼠模型中的生存能力方面的有效性。然后，我们将 sotorasib 施用于两名患有严重 G12C 相关动静脉畸形的成年患者。两名患者的症状和动静脉畸形大小均迅速减少。针对 KRAS G12C 似乎是一种有前途的治疗方法，适用于患有 G12C 相关血管畸形的患者。（由欧洲研究理事会等资助）。
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