Jakob Erdheim (1874-1937) first described craniopharyn-giomas (CPs) as "hypophyseal duct tumours" and postulated the existence of two tumour types based on their histological features: (1) an aggressive type showing similarities to adamantinomas (tumours of the jaw) and (2) a more benign form characterised by the presence of papillary structures. More than a century later, these initial observations have been confirmed; based on their distinct genetic, epigenetic, and histological features, the WHO classifies CPs into two types: adamantinomatous CPs (ACPs) and papillary CPs (PCPs). Considerable knowledge has been generated on the biology of CPs in the last 20 years. Mutations in CTNNB1 (encoding β-catenin) are prevalent in ACP, whilst PCPs frequently harbour mutations in BRAF (p.BRAF-V600E). The consequence of these mutations is the activation of either the WNT/β-catenin (ACP) or the MAPK/ERK (PCP) pathway. Murine models support a critical role for these mutations in tumour formation and have provided important insights into tumour pathogenesis, mostly in ACP. A critical role for cellular senescence has been uncovered in murine models of ACP with relevance to human tumours. Several gene profiling studies of human and murine ACP tumours have identified potential targetable pathways, and novel therapeutic agents are being used in clinical and pre-clinical research, in some cases with excellent results. In this review, we will present the accumulated knowledge on the biological features of these tumours and summarise how these advances are being translated into potential novel treatments.

中文翻译：

---

颅咽管瘤的生物学行为。


Jakob Erdheim (1874-1937) 首先将颅咽管肿瘤 (CP) 描述为“垂体导管肿瘤”，并根据其组织学特征推测存在两种肿瘤类型：(1) 侵袭性类型，与金刚质瘤（颌骨肿瘤）相似）和（2）一种更良性的形式，其特征是存在乳头状结构。一个多世纪后，这些最初的观察结果得到了证实。根据其独特的遗传、表观遗传和组织学特征，世界卫生组织将 CP 分为两类：金刚细胞 CP（ACP）和乳头状 CP（PCP）。在过去的 20 年里，人们对 CP 的生物学有了相当多的了解。 CTNNB1（编码 β-连环蛋白）的突变在 ACP 中普遍存在，而 PCP 经常在 BRAF (p.BRAF-V600E) 中存在突变。这些突变的结果是 WNT/β-连环蛋白 (ACP) 或 MAPK/ERK (PCP) 途径的激活。小鼠模型支持这些突变在肿瘤形成中的关键作用，并为肿瘤发病机制（主要是 ACP）提供了重要的见解。在与人类肿瘤相关的 ACP 小鼠模型中发现了细胞衰老的关键作用。人类和小鼠 ACP 肿瘤的几项基因分析研究已经确定了潜在的靶向途径，新型治疗剂正在临床和临床前研究中使用，在某些情况下取得了优异的结果。在这篇综述中，我们将介绍所积累的关于这些肿瘤生物学特征的知识，并总结这些进展如何转化为潜在的新疗法。