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

TLDR

Aberrant activation of intracellular signalling pathways, including JAK/STAT, confers malignant properties on cancer cells and has led to successful targeted therapies in haematological malignancies, with many solid tumours now also showing JAK/STAT activation. This review examines the role of JAK/STAT signalling in solid tumours, assessing how its activation contributes to oncogenesis and evaluating therapeutic prospects. The authors explore the molecular mechanisms driving inappropriate JAK/STAT activation and their cellular consequences, and consider how insights from haematological malignancies might inform solid tumour treatment strategies. Studies summarised in the review show that JAK/STAT activation influences prognosis across several tumour types.

Abstract

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.