RESUMO
The initial discovery of key developmental signalling pathways, largely using classical genetic approaches in model organisms, was followed by an intense burst of characterisation of the molecular components. Studies also began demonstrating a role for these pathways in oncogenesis. Patterns of mutations in Notch pathway components, such as those reported in subsets of hematological malignancies, have been easier to study, and the cumulative information is leading to potentially new therapies. However, it has been more challenging to clearly define the role of the Notch pathway in human solid tumours, given the absence of widespread specific activating or repressive mutations in key components of the pathway. In this review, we trace more than two decades of work looking at the role of Notch signalling in human cervical cancer progression. We document the contrasting reports on a tumour suppressive role and pro-oncogenic role in cervical cancers. However, an analysis of recent genomic data strikingly shows both widespread features of Notch expression and genetic changes that largely amplify positive regulators and delete negative controllers of the Notch pathway. This analysis reinforces a largely pro-oncogenic role for Notch signalling and lays the foundation for a nuanced exploration of synergistic and targeted therapies. Lastly, we further trace some of the complex challenges in advanced cervical cancer progression, including issues of cancer stem cells and metastasis.
