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.