摘要
神经胶质瘤也称脑胶质瘤,是神经系统中最常见的、疗效最差的恶性肿瘤。鼠类肉瘤病毒癌基因同源物B1(BRAF)突变在神经胶质瘤亚型中经常发生,其中BRAF V600突变最为常见,特别是上皮样胶质母细胞瘤(eGBM)、多形性黄星形细胞瘤(PXA)、间变性神经节神经胶质瘤(aGG)和儿童低级别星形细胞瘤。Ⅱ期临床试验VE-BASKET使用了BRAF抑制剂维莫非尼治疗BRAF V600突变型神经胶质瘤,初步证明了该药的有效性。对于BRAF V600E突变低级别胶质瘤(LGG)和高级别胶质瘤(HGG)患者,Ⅱ期临床试验NCT02034110证明了另一种BRAF抑制剂达拉非尼联合丝裂原活化细胞外信号调节激酶(MEK)抑制剂曲美替尼具有显著疗效。此研究表明,双靶治疗的疗效优于BRAF单靶治疗。另有NCT02124772 I/II期研究证明在年龄<18岁的复发/难治性BRAF V600突变LGG中,单独使用曲美替尼或联用达拉非尼均可达到安全可控的目标浓度,并且证明了临床疗效和耐受性。目前,美国食品药品监督管理局(FDA)已加速批准达拉非尼联合曲美替尼用于治疗具有BRAF V600E突变的6岁及以上不可切除或转移性实体肿瘤的患者以及治疗一岁及以上需要全身治疗的LGG儿童患者。该文将聚焦于BRAF V600突变神经胶质瘤患者,对其临床/病理学特征及治疗进展进行系统阐述。
Glioma,also known as brain glioma,is the most common and least effective malignant tumor in the nervous system.V-Raf murine sarcoma viral oncogene homolog B1(BRAF)mutation occurs frequently in glioma subtypes,of which BRAF V600 mutation is the most common,in particular,epithelioid glioblastoma(eGBM),pleomorphic yellow astrocytoma(PXA),anaplastic ganglioglioma(aGG),and low-grade astrocytoma in children.The phase II trial of VE-BASKET used the BRAF inhibitor vemurafenib in the treatment of BRAF V600 mutant glioma,and initially demonstrated the effectiveness of the drug.For patients with low-grade glioma(LGG)and high-grade glioma(HGG)with BRAF V600E mutations,the phase II clinical trial NCT02034110 demonstrated the efficacy of dabrafenib,another BRAF inhibitor,in combination with the mitogen-activated extracellular signal-regulated kinase(MEK)inhibitor,trametinib.The study showed that the efficacy of dual-target therapy was superior to BRAF single-target therapy.Another phase I/II study,NCT02124772,demonstrated safe and controllable target concentrations of trametinib alone or in combination with dabrafenib in relapsed/refractory BRAF V600 mutant LGG patients<18 years of age,and demonstrated clinical efficacy and tolerability.Currently,the U.S.Food and Drug Administration(FDA)has accelerated approval of dabrafenib in combination with trametinib for the treatment of unresectable or metastatic solid tumors with the BRAF V600E mutation and 6 years of age and older and for the treatment of LGG children who require systemic therapy with 1 year of age and older.The article will focus on patients with BRAF V600 mutated glioma and systematically describe their clinical and pathological features and treatment progress.
作者
李杨
彭丽丽
康曦匀
梁金龙
步玉晴
张洪珍
LI Yang;PENG Lili;KANG Xiyun;LIANG Jinlong;BU Yuqing;ZHANG Hongzhen(Graduate School,North China University of Science and Technology,Hebei Tangshan 063210,China;The Fifth Department of Oncology,Hebei General Hospital,Hebei Shijiazhuang 050051,China;Graduate School,Hebei North University,Hebei Zhangjiakou 075000,China)
出处
《现代肿瘤医学》
CAS
2024年第12期2271-2275,共5页
Journal of Modern Oncology
基金
河北省重点研发计划项目-卫生健康创新专项(编号:21377795D)。
