The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) cell signaling pathway functions as part of gene transcription and immune regulation. JAK1/2/3 are intracellular tyrosine kinases, whereas STAT1/2/3 are transcription factors that activate gene expression. The JAK/STAT pathway is activated by the binding of a ligand, such as interleukins, interferons, or growth factors, to specific cell surface receptors, which then convey signals downstream through the JAK/STAT pathway. 
Figure 1. Receptor tyrosine kinases can promote activation of Janus kinases (JAK-1/-2/-3). Janus kinases auto-phosphorylate and recruit signal transducers and activators of transcription (STAT-1/-2/-3/-4/-5/-6). Phosphorylated STAT (-1/-2/-3/-4/-5/-6) proteins dimerize. The STAT (-1/-2/-3/-4/-5/-6) dimer enters the nucleus where it binds to DNA to activate gene transcription, regulate immunity, and promote cell growth and survival. Specific nodes in the pathway that are therapeutically actionable are noted.
Biomarkers in the JAK/STAT signaling pathway serve as inclusion eligibility criteria in 29 clinical trials, of which 17 are open and 12 are closed. The genes JAK2, JAK3, JAK1, CRLF2, and STAT3 on this pathway most frequently harbor alterations that are inclusion eligibility criteria for clinical trials.
Of the trials that contain alteration(s) in the JAK/STAT signaling pathway as inclusion criteria, 1 is early phase 1 (1 open), 5 are phase 1 (2 open), 4 are phase 1/phase 2 (3 open), 16 are phase 2 (9 open), 1 is phase 2/phase 3 (1 open), and 2 are phase 3 (1 open) .