The medical therapy of craniopharyngiomas: the way ahead

Research output: Contribution to journalReview article

Authors

Colleges, School and Institutes

External organisations

  • University of Oxford

Abstract

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. Evidence Acquisition: 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]). Evidence Synthesis: 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. Conclusions: 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.

Details

Original languageEnglish
Pages (from-to)5751–5764
Number of pages14
JournalJournal of Clinical Endocrinology and Metabolism
Volume104
Issue number12
Early online date1 Aug 2019
Publication statusPublished - Dec 2019