JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects
By Shubhasree Banerjee, A. Biehl, M. Gadina, S. Hasni, D. Schwartz. Drugs, 2017
1,029 citations recorded by the source corpus.
The Janus kinase/signal transduction and activator of transcription (JAK–STAT) signaling pathway is implicated in the pathogenesis of inflammatory and autoimmune diseases including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Many cytokines involved in the pathogenesis of autoimmune and inflammatory diseases use JAKs and STATs to transduce intracellular signals. Mutations in JAK and STAT genes cause a number of immunodeficiency syndromes, and polymorphisms in these genes are associated with autoimmune diseases. The success of small-molecule JAK inhibitors (Jakinibs) in the treatment of rheumatologic disease demonstrates that intracellular signaling pathways can be targeted therapeutically to treat autoimmunity. Tofacitinib, the first rheumatologic Jakinib, is US Food and Drug Administration (FDA) approved for rheumatoid arthritis and is currently under investigation for other autoimmune diseases. Many other Jakinibs are in preclinical development or in various phases of clinical trials. This review describes the JAK–STAT pathway, outlines its role in autoimmunity, and explains the rationale/pre-clinical evidence for targeting JAK–STAT signaling. The safety and clinical efficacy of the Jakinibs are reviewed, starting with the FDA-approved Jakinib tofacitinib, and continuing on to next-generation Jakinibs. Recent and ongoing studies are emphasized, with a focus on emerging indications for JAK inhibition and novel mechanisms of JAK–STAT signaling blockade.
Subfields: Genetics, Oncology, Rheumatology
View Paper: https://www.semanticscholar.org/paper/277575898ce3b2eee6789233fc65d439c15858a2
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Citations in the corpus
- Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer (2018, background): “In particular, our PARADIGM analysis showed that C3:mesenchymal (immune) and C20:mixed (stromal/immune) tumors shared upregulated JAK2/STAT1,3,6 signaling with C14:LUAD tumors and C10:pan-SCC, pointing to the possibility of treating these diverse iCluster tumors with JAK-STAT agents currently approv”
- PD-1/PD-L1 pathway: current researches in cancer. (2020, background): “JAK signaling activation of the STAT pathway is an evolutionarily conserved signaling pathway used by a variety of cytokines, IFNs, growth factors and related molecules [36].”