Abstract
The JAK-STAT pathway plays a central role in cell proliferation, differentiation, survival, and embryological processes. Aberrant activation of the JAK-STAT pathway due to genetic mutations, amplifications, or polymorphisms can lead to constitutive or persistent activation of the pathway and affect the development of some cancers. In this review, we discuss the major signaling molecules involved in the JAK-STAT pathway and their role in hematologic malignancies and solid tumors. In addition, we discuss FDA-approved drugs and other JAK-STAT pathway inhibitors that are in clinical trials or under preclinical development. Despite recent developments in our understanding of the JAK-STAT pathway, it remains to be determined precisely how the JAK-STAT pathway drives tumor development and oncogenic phenotypes. Due to the complex cross talk of the JAK-STAT pathway with other signaling pathways, further studies exploring the direct role and contribution of the JAK-STAT pathway toward tumor initiation and development are needed. These studies should illuminate whether treatment with JAK inhibitors alone or in combination with inhibitors that target complimentary signaling pathways can be therapeutic in cancer patients and which patients are most likely to benefit.
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References
O’Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med. 2015;66:311–28.
Thomas SJ, Snowden JA, Zeidler MP, Danson SJ. The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours. Br J Cancer. 2015;113(3):365–71.
Pencik J, Pham HT, Schmoellerl J, Javaheri T, Schlederer M, Culig Z, et al. JAK-STAT signaling in cancer: from cytokines to non-coding genome. Cytokine. 2016;87:26–36.
Lim CP, Cao X. Structure, function, and regulation of STAT proteins. Mol BioSyst. 2006;2(11):536–50.
Buchert M, Burns CJ, Ernst M. Targeting JAK kinase in solid tumors: emerging opportunities and challenges. Oncogene. 2016;35(8):939–51.
Constantinescu SN, Girardot M, Pecquet C. Mining for JAK-STAT mutations in cancer. Trends Biochem Sci. 2008;33(3):122–31.
Balko JM, Schwarz LJ, Luo N, Estrada MV, Giltnane JM, Davila-Gonzalez D, et al. Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence. Sci Transl Med. 2016;8(334):334ra53.
Silver-Morse L, Li WX. JAK-STAT in heterochromatin and genome stability. Jak Stat. 2013;2(3):e26090.
Kontzias A, Kotlyar A, Laurence A, Changelian P, O’Shea JJ. Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease. Curr Opin Pharmacol. 2012;12(4):464–70.
Sonbol MB, Firwana B, Zarzour A, Morad M, Rana V, Tiu RV. Comprehensive review of JAK inhibitors in myeloproliferative neoplasms. Ther Adv Hematol. 2013;4(1):15–35.
Chen X, Vinkemeier U, Zhao Y, et al. Crystal structure of a tyrosine phosphorylated STAT1 dimer bound to DNA. Cell. 1998;93:827–39.
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Luo, N., Balko, J.M. (2019). Role of JAK-STAT Pathway in Cancer Signaling. In: Badve, S., Kumar, G. (eds) Predictive Biomarkers in Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-95228-4_26
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DOI: https://doi.org/10.1007/978-3-319-95228-4_26
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