The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours

Aberrant activation of intracellular signalling pathways confers malignant properties on cancer cells. Targeting intracellular signalling pathways has been a productive strategy for drug development, with several drugs acting on signalling pathways already in use and more continually being developed. The JAK/STAT signalling pathway provides an example of this paradigm in haematological malignancies, with the identification of JAK2 mutations in myeloproliferative neoplasms leading to the development of specific clinically effective JAK2 inhibitors, such as ruxolitinib. It is now clear that many solid tumours also show activation of JAK/STAT signalling. In this review, we focus on the role of JAK/STAT signalling in solid tumours, examining the molecular mechanisms that cause inappropriate pathway activation and their cellular consequences. We also discuss the degree to which activated JAK/STAT signalling contributes to oncogenesis. Studies showing the effect of activation of JAK/STAT signalling upon prognosis in several tumour types are summarised. Finally, we discuss the prospects for treating solid tumours using strategies targeting JAK/STAT signalling, including what can be learned from haematological malignancies and the extent to which results in solid tumours might be expected to differ