Targeting the JAK/STAT signalling axis in cancer: chemopreventive potential of natural compounds with emerging focus on retinoids.

Aberrant activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway, particularly STAT3, contributes to tumour progression, metastasis, immune evasion, and therapeutic resistance, making it an attractive target for cancer prevention and therapy. Numerous natural compounds have been reported to modulate this pathway in preclinical studies; however, their clinical translation remains constrained by limited mechanistic validation and poor pharmacokinetic properties. Retinoids, well established as regulators of cellular differentiation and proliferation, have recently emerged as potential modulators of JAK/STAT signalling, although the molecular basis of this interaction remains poorly understood. This review critically evaluates current evidence linking natural compounds with JAK/STAT inhibition, with particular emphasis on the emerging retinoidJAK/STAT interface. By distinguishing established findings from hypothesis-generating observations, identifying key mechanistic gaps, and outlining future experimental priorities, this review provides a framework for evaluating the therapeutic potential of retinoid-mediated JAK/STAT modulation in cancer.