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Inhibitors of the JAK/STAT Pathway, with a Focus on Ruxolitinib and Similar Agents

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Resistance of Targeted Therapies Excluding Antibodies for Lymphomas

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 17))

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Abstract

Substantive advances in our understanding of the pathogenesis of different types of lymphoma have arisen with the advent of methodologies to interrogate the genome, epigenome, and transcriptome of tumor cells. Amongst the most frequently perturbed intracellular signaling pathways identified in lymphoma is the JAK/STAT pathway, which has also been implicated in the pathogenesis of other blood cancers. Acquired mutations may affect this pathway by activating members of the JAK and STAT families directly, by inactivating those proteins whose normal function is to deactivate the JAKs, or by establishing autocrine signaling loops that drive JAK-mediated proliferation. The utilization of inhibitors of JAK/STAT activation may therefore benefit those individuals with lymphoma that are not served adequately by conventional therapies. Two JAK inhibitors, tofacitinib and ruxolitinib, are approved for use in humans currently, whilst others are under evaluation in clinical trials, and more efficacious drugs are being developed. The nature and therapeutic potential of these compounds in the treatment of patients with lymphoma are discussed.

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  1. The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia

    Linda M. Scott

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  1. Department of Onco-Hematology, Unit of Lymphoid Malignancies, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Andrés J. M. Ferreri

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Scott, L.M. (2018). Inhibitors of the JAK/STAT Pathway, with a Focus on Ruxolitinib and Similar Agents. In: Ferreri, A. (eds) Resistance of Targeted Therapies Excluding Antibodies for Lymphomas. Resistance to Targeted Anti-Cancer Therapeutics, vol 17. Springer, Cham. https://doi.org/10.1007/978-3-319-75184-9_6

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