The JAK/STAT Signaling Pathway in Cancer: Mechanisms, Roles, and Therapeutic Implications

Abstract

The JAK/STAT signaling pathway regulates processes such as proliferation, differentiation, survival, and immune responses. Dysregulation of this pathway is strongly correlated with the initiation and progression of several malignancies in humans. This pathway consists of Janus Kinases (JAKs) and Signal Transducers and Activators of Transcription (STATs), which together form a signaling network with feedback regulation and extensive crosstalk with other oncogenic pathways. Cytokine stimulation leads to JAK-mediated phosphorylation, activating STAT proteins, allowing them to dimerize and translocate to the nucleus, where they regulate the transcription of genes involved in angiogenesis, immune evasion, survival, and tumor growth. Hematological malignancies and solid tumours exhibit persistent activation of JAK/STAT signaling, highlighting its role in cancer. Errors in this signaling pathway cause sustained proliferative signaling, apoptosis resistance, and modulation of the tumour microenvironment, all of which eventually lead to tumorigenesis. Therefore, targeting this pathway is a promising therapeutic strategy for treating cancer. Several JAK inhibitors have been developed and clinically approved, demonstrating their efficacy in suppressing downstream STAT activation.