Endocrine Unit, 1st Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
J Clin Endocrinol Metab. 2019 Dec 1;104(12):5751-5764. doi: 10.1210/jc.2019-01299.
Craniopharyngiomas, which are categorized as adamantinomatous (ACPs) or papillary (PCPs), have traditionally been treated with surgery and/or radiotherapy, although when the tumors progress or recur, therapeutic possibilities are very limited. Following recent advances in their molecular pathogenesis, new medical therapeutic options have emerged.
The search strategy that we selected to identify the appropriate evidence involved the following medical subject headings (MeSH) terms: ("Craniopharyngioma" [MeSH] AND "Craniopharyngioma/drug therapy" [MeSH]) NOT ("review" [Publication Type] OR "review literature as topic" [MeSH Terms] OR "review" [All Fields]) AND ("2009/05/01" [PDat]: "2019/04/28" [PDat]).
Mutations of β-catenin causing Wnt activation with alterations of the MEK/ERK pathway are encountered in the great majority of patients with ACPs; specific alterations also stratify patients to a more aggressive behavior. In most PCPs there is primary activation of the Ras/Raf/MEK/ERK pathway secondary to BRAF-V600E mutations. BRAF inhibitors, such as dabrafenib or vemurafenib, either alone or in combination with the MEK inhibitors trametinib and cobimetinib, have been administered to patients with PCPs producing clinically useful and, in some cases, sustained responses. In contrast to PCPs, drugs targeting β-catenin and its downstream MAPK pathway in ACPs have so far only been used in in vitro studies, but there appear to be promising new targets clinically.
The identification of specific genetic alterations in patients with craniopharyngiomas has expanded the therapeutic options, providing evidence for a customized approach using newer molecular agents. More studies including a larger number of carefully selected patients are required to evaluate the response to currently available and evolving agents alone and in combination.
颅咽管瘤分为造釉细胞瘤（ACPs）或乳头瘤（PCPs），传统上采用手术和/或放疗治疗，尽管当肿瘤进展或复发时，治疗选择非常有限。随着分子发病机制的最新进展，出现了新的医学治疗选择。
我们选择的用于确定适当证据的搜索策略涉及以下医学主题词（MeSH）术语：（“颅咽管瘤”[MeSH]和“颅咽管瘤/药物治疗”[MeSH]）而不是（“综述”[出版类型]或“综述文献作为主题”[MeSH 术语]或“综述”[所有字段]）和（“2009/05/01”[PDat]：“2019/04/28”[PDat]）。
β-连环蛋白的突变导致 Wnt 激活，并伴有 MEK/ERK 通路的改变，在绝大多数 ACP 患者中都有发现；特定的改变也使患者具有更具侵袭性的行为。在大多数 PCP 中，由于 BRAF-V600E 突变，Ras/Raf/MEK/ERK 通路会被原发性激活。BRAF 抑制剂，如 dabrafenib 或 vemurafenib，单独或与 MEK 抑制剂 trametinib 和 cobimetinib 联合使用，已用于治疗 PCP 患者，产生了临床有用的反应，在某些情况下，反应可持续。与 PCP 不同，针对 ACP 中β-连环蛋白及其下游 MAPK 通路的药物迄今为止仅在体外研究中使用，但临床上似乎有新的有前途的靶点。
在颅咽管瘤患者中鉴定出特定的遗传改变，扩大了治疗选择，为使用新型分子药物提供了个性化治疗方法的证据。需要更多包括更多精心挑选的患者的研究来评估目前可用和不断发展的药物单独和联合使用的反应。
