Role of Janus kinase-signal transducer and activator of transcription signaling pathway in hormonal cancer therapeutic resistance and lineage plasticity.

Cancers of the breast and prostate are one of the leading causes of cancer deaths in women and men, respectively. Although several treatment options have been developed to transform these cancers into manageable chronic diseases, they still contribute to over 70 000 deaths each year in the United States. Though majority of these cancers belong to slow growing differentiated subtypes, the cancers evolve over time due to treatment-related pressure into aggressive treatment-resistant types. A mechanism attributed to the transformation of hormonal and other cancers into aggressive treatment-refractory cancers is "lineage plasticity," a term used to describe a switch in the cell type or lineage. Evolving evidences suggest that the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway plays a key role in driving lineage plasticity. This review discusses the role of JAK-STAT signaling pathway in hormonal cancers' evolution into aggressive cancers and in treatment resistance, with focus on treatment-induced lineage plasticity.