INOVA, Schar Cancer Institute, Fairfax, VA, USA.
UVA School of Medicine, INOVA Fairfax Medical Campus, Fairfax, VA, USA.
Drugs R D. 2024 Sep;24(3):395-403. doi: 10.1007/s40268-024-00475-5. Epub 2024 Aug 23.
While successful treatment paradigms for BRAF V600 mutations have been developed, 10% of BRAF mutations are not at V600 and lack a standard treatment regimen. This study summarizes the current body of knowledge on the treatment of non-V600 mutations and reports a single institution experience.
We conducted a literature review to summarize relevant preclinical and clinical published data on the response of non-V600 mutations to targeted therapies. We performed a retrospective analysis of INOVA Schar Cancer patients registered in our Molecular Tumor Board database with non-V600 BRAF mutations who were recipients of targeted therapy and assessed their time to next treatment and best response.
Published preclinical and clinical data have demonstrated limiting results in the response of non-V600 mutated cancers to targeted therapies. Response rates were variable for the major classes of BRAF mutations including class II and class III mutations as well as, BRAF fusions. Data collected from our INOVA cohort offered promising results with one patient achieving partial remission and two patients achieving stable disease.
This article reflects the current understanding of targeted therapies in non-V600 mutations. Further large-scale studies separating BRAF mutations based on their mechanism of activation will expand our understanding.
虽然已经开发出针对 BRAF V600 突变的成功治疗方案，但仍有 10%的 BRAF 突变并非 V600 突变，且缺乏标准的治疗方案。本研究总结了目前关于非 V600 突变治疗的知识体系，并报告了一家机构的经验。
我们进行了文献综述，以总结关于非 V600 突变对靶向治疗反应的相关临床前和临床发表数据。我们对 INOVA Schar 癌症患者进行了回顾性分析，这些患者在我们的分子肿瘤委员会数据库中登记，具有非 V600 BRAF 突变，接受了靶向治疗，并评估了他们的下一次治疗时间和最佳反应。
已发表的临床前和临床数据表明，非 V600 突变型癌症对靶向治疗的反应有限。主要 BRAF 突变类别（包括 II 类和 III 类突变以及 BRAF 融合）的反应率各不相同。从我们的 INOVA 队列收集的数据提供了有希望的结果，一名患者实现部分缓解，两名患者实现稳定疾病。
本文反映了目前对非 V600 突变的靶向治疗的理解。进一步基于激活机制对 BRAF 突变进行大规模研究将扩大我们的认识。
