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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