Department of Neurology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Department of Pathology, Johns Hopkins University; Department of Radiology and Radiological Science, Johns Hopkins Hospital; and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
J Natl Compr Canc Netw. 2018 Apr;16(4):343-347. doi: 10.6004/jnccn.2017.7052.
V600 mutations are being identified in patients with primary brain tumors more often as molecular testing becomes widely available. Targeted treatment with BRAF inhibitors has been attempted in individual cases with some responses, whereas others showed no response or developed resistance. Preclinical work suggests that gliomas could be more responsive to the concurrent use of BRAF and MEK inhibition for MAP kinase pathway suppression. This report presents 2 cases of malignant brain tumors with V600E mutations that were resistant to radiation and temozolomide, and reports on their response to targeted treatment with the BRAF and MEK inhibitors dabrafenib and trametinib. One patient with an anaplastic pleomorphic xanthoastrocytoma experienced a partial response for 14 months, demonstrated by progressive tumor shrinkage and clinical improvement; however, this was followed by clinical and radiographic progression. The patient with glioblastoma continued to have stable disease after 16 months of treatment. These cases are encouraging in a disease that urgently needs new treatments. Further work is necessary to understand response rates, duration, and survival in primary brain tumors.
随着分子检测的广泛应用，越来越多的原发性脑肿瘤患者被发现存在 V600 突变。针对 BRAF 抑制剂的靶向治疗已在个别病例中进行了尝试，部分病例有一定的反应，而其他病例则没有反应或产生了耐药性。临床前研究表明，BRAF 和 MEK 抑制联合抑制 MAP 激酶通路可能使神经胶质瘤更敏感。本报告介绍了 2 例 V600E 突变的恶性脑肿瘤患者，这些患者对放疗和替莫唑胺耐药，并报告了他们对 BRAF 和 MEK 抑制剂达拉非尼和曲美替尼的靶向治疗的反应。一名间变性多形性黄色星形细胞瘤患者经历了 14 个月的部分缓解，表现为肿瘤逐渐缩小和临床改善；然而，随后出现了临床和影像学进展。胶质母细胞瘤患者在治疗 16 个月后仍保持疾病稳定。在这种急需新治疗方法的疾病中，这些病例令人鼓舞。还需要进一步的研究来了解原发性脑肿瘤的反应率、持续时间和生存率。
