60 YEARS OF NEUROENDOCRINOLOGY: Biology of human craniopharyngioma: lessons from mouse models

    1. Juan Pedro Martinez-Barbera
    1. Developmental Biology and Cancer Programme, Institute of Child Health, Birth Defects Research Centre, University College London, 30 Guilford Street, WC1N 1EH London, UK
    1. Correspondence should be addressed to J P Martinez-Barbera; Email: j.martinez-barbera{at}ucl.ac.uk


    Adamantinomatous craniopharyngiomas (ACP) are clinically relevant tumours that are associated with high morbidity, poor quality of life and occasional mortality. Human and mouse studies have provided important insights into the biology of these aggressive tumours, and we are starting to understand why, how and when these tumours develop in humans. Mutations in β-catenin that result in the over-activation of the WNT/β-catenin signalling pathway are critical drivers of most, perhaps of all, human ACPs. Mouse studies have shown that only pituitary embryonic precursors or adult stem cells are able to generate tumours when targeted with oncogenic β-catenin, which suggests that the cell context is critical in order for mutant β-catenin to exert its oncogenic effect. Interestingly, mutant stem cells do not generate the bulk of the tumour cells; instead, they induce tumours in a paracrine manner. Combining basic studies in mice and humans will provide further insights into the biology of these neoplasms and will reveal pathogenic pathways that could be targeted with specific inhibitors for the benefit of patients. These benign tumours may additionally represent a unique model for investigating the early steps that lead to oncogenesis.

    • Received in final form 21 April 2015
    • Accepted 29 April 2015
    • Made available online as an Accepted Preprint 29 April 2015
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