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Qureshy et al. J Cancer Metastasis Treat 2020;6:27 Journal of Cancer
DOI: 10.20517/2394-4722.2020.58 Metastasis and Treatment

Review Open Access

Targeting the JAK/STAT pathway in solid tumors

Zoya Qureshy, Daniel E. Johnson, Jennifer R. Grandis

Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco 94158, USA.

Correspondence to: Dr. Jennifer R. Grandis, Department of Otolaryngology-Head and Neck Surgery, University of California San
Francisco, San Francisco 94158, USA. E-mail: jennifer.grandis@ucsf.edu

How to cite this article: Qureshy Z, Johnson DE, Grandis JR.Targeting the JAK/STAT pathway in solid tumors. J Cancer Metastasis
Treat 2020;6:27. http://dx.doi.org/10.20517/2394-4722.2020.58

Received: 10 Jun 2020 First Decision: 15 Jun 2020 Revised: 17 Jul 2020 Accepted: 27 Jul 2020 Published: 21 Aug 2020
Academic Editor: William P. Schiemann Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Aberrant activation of signal transducer and activator of transcription (STAT) proteins is associated with the
development and progression of solid tumors. However, as transcription factors, these proteins are difficult to
target directly. In this review, we summarize the role of targeting Janus kinases (JAKs), upstream activators of
STATs, as a strategy for decreasing STAT activation in solid tumors. Preclinical studies in solid tumor cell line
models show that JAK inhibitors decrease STAT activation, cell proliferation, and cell survival; in in vivo models,
they also inhibit tumor growth. JAK inhibitors, particularly the JAK1/2 inhibitor ruxolitinib, sensitize cell lines and
murine models to chemotherapy, immunotherapy, and oncolytic viral therapy. Ten JAK inhibitors have been or
are actively being tested in clinical trials as monotherapy or in combination with other agents in patients with
solid tumors; two of these inhibitors are already Food and Drug Administration (FDA) approved for the treatment
of myeloproliferative disorders and rheumatoid arthritis, making them attractive agents for use in patients with
solid tumors as they are known to be well-tolerated. Four JAK inhibitors (two of which are FDA approved for other
indications) have exhibited promising anti-cancer effects in preclinical studies; however, clinical studies specifically
assessing their activity against the JAK/STAT pathway in solid tumors have not yet been conducted. In summary,
JAK inhibition is a viable option for targeting the JAK/STAT pathway in solid tumors and merits further testing in
clinical trials.

Keywords: Clinical trials, Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, JAK
inhibitors, solid tumors, STAT hyperactivation

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
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