Department of Oral and Plastic Maxillofacial Surgery, Military Hospital Ulm, Academic Hospital of the University of Ulm, Oberer Eselsberg 40, 89081, Ulm, Germany.
Department of Oral and Plastic Maxillofacial Surgery, University Hospital Ulm, Albert-Einstein-Allee 10, 89081, Ulm, Germany.
Med Oncol. 2023 Apr 28;40(6):163. doi: 10.1007/s12032-023-01993-z.
Ameloblastoma in 66% of the cases harbor a somatic mutation of the "mitogen-activated protein kinase" signaling pathway (BRAF V600E). In V600E mutations, BRAF is in the permanent "on" state and relays the growth-promoting signals independently of the EGFR pathway. Therefore, mutant BRAF represents a target for handful of new drugs.
We conducted a literature search, with the search terms "Vemurafenib, Dabrafenib, Ameloblastoma, and BRAF." These included seven case reports with nine patients who underwent monotherapy with Dabrafenib or Vemurafenib or combination therapy with Dabrafenib and Trametinib.
The patients age ranges from 10 years up to 86 years. The distribution of women and men is 4:5. Patients with an initial diagnosis of ameloblastoma, as well as recurrences or metastasized ameloblastoma were treated. Indications cover neoadjuvant therapy up to the use in metastasized patients in an irresectable state. Results ranging from "only" tumor size reduction to restitutio ad integrum.
We see the use of BRAF Inhibitors to reduce tumor size with consecutive surgical treatment as a reasonable option for therapy. However, we are aware that at present the data are based only on case reports with the longest follow-up of just 38 months. We encourage further clinical trials in the use of BRAF Inhibitors for selecting ameloblastoma patients in a multi-center setting.
66%的成釉细胞瘤患者携带“丝裂原活化蛋白激酶”信号通路（BRAF V600E）的体细胞突变。在 V600E 突变中，BRAF 处于永久“开启”状态，并独立于 EGFR 通路传递促生长信号。因此，突变 BRAF 成为少数几种新药的靶点。
我们进行了文献检索，检索词为“Vemurafenib、Dabrafenib、Ameloblastoma 和 BRAF”。这些文献包括 7 个病例报告，共 9 例患者接受了 Dabrafenib 或 Vemurafenib 单药治疗或 Dabrafenib 和 Trametinib 联合治疗。
患者年龄范围为 10 岁至 86 岁。女性和男性的分布比例为 4:5。治疗的患者既有初诊为成釉细胞瘤的，也有复发或转移的成釉细胞瘤。适应证涵盖新辅助治疗，直至转移性不可切除患者的应用。结果从“仅”肿瘤缩小到完全恢复。
我们认为，使用 BRAF 抑制剂缩小肿瘤体积并随后进行手术治疗是一种合理的治疗选择。然而，我们意识到目前的数据仅基于病例报告，最长随访时间仅为 38 个月。我们鼓励在多中心环境中进一步开展临床试验，以选择成釉细胞瘤患者使用 BRAF 抑制剂。
