Endocrine Abstracts

Adamantinomatous craniopharyngioma (ACP) is a paediatric pituitary tumour that is associated with high morbidity due to the tendency of the tumour to infiltrate locally into surrounding brain structures such as the hypothalamus and visual tracts. We have developed mouse models for human ACP, which we are using to better understand the pathogenesis of these human tumours as well as to test novel targeted treatments. Using advanced imaging techniques such as X-ray computed tomography (micro-CT) and magnetic resonance imaging (MRI), we show that mouse and human tumours display similar radiological features and reveal insights into the invasive properties of the human tumours. Complementing our initial molecular studies on murine ACP, we have now completed whole-transcriptomic analysis of 18 samples of human ACP (16 pediatric, one adult) and six control samples. Together, mouse and human studies indicate that the paracrine activities of senescent cells may be critical for tumour initiation and growth. The molecular studies have also identified several dysregulated pathways, offering potential new targets against human ACP, which are currently being investigated in ongoing pre-clinical trials. Of note, inhibition of the sonic hedgehog (SHH) pathway, activated in both murine and human ACP, provides no benefit to the treated mice. In contrast, pathway inhibition leads to faster progression of the tumours.