ABSTRACT The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is a critical communication hub that translates extracellular signals into gene expression programs. Its aberrant activation serves as a central driver of tumorigenesis, metastasis, and immunosuppression in diverse malignancies. With research expanding from hematologic malignancies to solid tumors, the JAK/STAT pathway has gradually emerged as a promising therapeutic target for cancer treatment. This review systematically analyzes the multi‐dimensional dysregulation of the JAK/STAT pathway, encompassing somatic mutations, epigenetic modifications, and aberrant cytokine networks. We elucidate critical non‐canonical functions that underpin metabolic reprogramming and chromatin stability. Furthermore, we detail the pathway's pivotal role in bridging tumor cells with the microenvironment, focusing on myeloid‐derived suppressor cells (MDSC) recruitment and the reciprocal STAT3/PD‐L1 axis that fuels immune evasion and therapeutic resistance. Finally, we comprehensively evaluate the shifting therapeutic landscape, advocating for a transition from broad‐spectrum kinase inhibitors to high‐precision modalities such as allosteric modulators, proteolysis targeting chimeras (PROTACs), and novel combination strategies. By integrating the advance in the JAK/STAT pathway with cancer, this review underscores the potential of targeting this signaling axis for cancer therapy.
Liao et al. (Sun,) studied this question.
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