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JAK-STAT pathway targeting for the treatment of inflammatory bowel disease. | LitMetric

AI Article Synopsis

  • - Cytokines play a crucial role in maintaining intestinal balance and are key players in inflammatory bowel diseases (IBD) like Crohn's disease and ulcerative colitis, acting through specific signaling pathways (JAK-STAT).
  • - While current treatments targeting individual cytokines have improved IBD management, there's a need for broader solutions for patients who don't respond well to these therapies.
  • - New small-molecule JAK inhibitors, including tofacitinib (approved for ulcerative colitis), are being developed to target multiple inflammatory pathways, with ongoing research into their effectiveness, safety, and treatment optimization strategies.

Article Abstract

Cytokines are involved in intestinal homeostasis and pathological processes associated with inflammatory bowel disease (IBD). The biological effects of cytokines, including several involved in the pathology of Crohn's disease and ulcerative colitis, occur as a result of receptor-mediated signalling through the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) DNA-binding families of proteins. Although therapies targeting cytokines have revolutionized IBD therapy, they have historically targeted individual cytokines, and an unmet medical need exists for patients who do not respond to or lose response to these treatments. Several small-molecule inhibitors of JAKs that have the potential to affect multiple pro-inflammatory cytokine-dependent pathways are in clinical development for the treatment of IBD, with one agent, tofacitinib, already approved for ulcerative colitis and several other agents with demonstrated efficacy in early phase trials. This Review describes the current understanding of JAK-STAT signalling in intestinal homeostasis and disease and the rationale for targeting this pathway as a treatment for IBD. The available evidence for the efficacy, safety and pharmacokinetics of JAK inhibitors in IBD as well as the potential approaches to optimize treatment with these agents, such as localized delivery or combination therapy, are also discussed.

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Source
http://dx.doi.org/10.1038/s41575-020-0273-0DOI Listing

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