Abstract
Craniopharyngiomas are rare epithelial tumours arising along the path of the craniopharyngeal duct. Two major histological subtypes have been recognised, the papillary and the adamantinomatous. Craniopharyngiomas remain challenging tumours to manage and are associated with significant morbidities and mortality. Recent advances in the molecular pathology of these neoplasms have identified BRAF mutations in the papillary variant, offering promising options for targeted pharmacological treatment. The involvement of β-catenin and the Wnt pathway in the tumorigenesis of the adamantinomatous subtype has been previously established with the identification of stabilising mutations in exon 3 of CTNNB1. Further understanding of the pathogenesis of this subtype has been facilitated with the use of mouse models and xenograft experiments. It has been proposed that the clusters of cells with upregulated Wnt/β-catenin signalling induce tumour formation in a paracrine manner; the complex interactions occurring between different cell populations need to be further clarified for further expansion of this hypothesis. This review outlines recent key advances in our understanding of the molecular pathology of craniopharyngiomas and discusses some of the challenges that need to be overcome for the development of targeted therapies that will hopefully improve the management and the outcomes of these patients.
Highlights
Craniopharyngiomas (CPs) are epithelial tumours (WHO grade I) arising along the path of the craniopharyngeal duct
The identification of BRAF (V600E) mutations in pCP has led to the potential for new targeted pharmacological therapy
Our understanding of aCP has been greatly improved by mouse model and xenograft experiments revealing new and critical roles for β-catenin-accumulating cluster cells; there is still
Summary
Craniopharyngiomas (CPs) are epithelial tumours (WHO grade I) arising along the path of the craniopharyngeal duct (embryonal structure connecting stomodeal ectoderm and the evaginated Rathke’s pouch). The resulting daughter cells form the β-catenin-accumulating clusters that are characteristic of aCP These clusters become quiescent and secretory, signalling by means of secretory proteins including members of the fibroblast growth factor (FGF), transforming growth factor beta (TGFβ), epithelial growth factor, and SHH pathways, along with pro-inflammatory cytokines and chemokines,[30] to induce transformation in surrounding cells and perhaps modify the tumour microenvironment. While the discovery of the BRAF (V600E) mutation in pCP has afforded us an opportunity for a promising pharmacological intervention, recent progress in understanding aCP reveals a morphologically complex tumour with distinct cell populations that have differing functions and cells of origin. Much to clarify about the complex interactions that occur between different cell populations within this neoplasm before we are in the position to develop effective targeted therapies
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