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JAK plays an important role in the formation and development of blood cells, and defects in the gene have been identified in myeloproliferative neoplasms.
Though researchers have been aware of the Janus kinase (JAK) signaling pathway and its role in cellular processes for several decades, it was not until 2005 that mutations in the JAK gene were linked directly to the development of cancers. JAK plays an important role in the formation and development of blood cells, and defects in the gene have been identified in myeloproliferative neoplasms.
As a result, JAK inhibitors for the treatment of hematologic malignancies have been an intense research focus, with one drug receiving approval in 2011 and several more in various stages of clinical development.
In November, the FDA approved ruxolitinib (Jakafi; Incyte) for the treatment of intermediate or high-risk myelofibrosis, in which dysregulation of the JAK1 and JAK2 pathways results in a depletion of healthy bone marrow that burdens the liver and spleen.
In the phase III COMFORT-I study, 41.9% of patients receiving ruxolitinib had at least a 35% reduction in spleen size, and 45.9% of patients on the drug reported a reduction in symptoms.
Other JAK inhibitors are being assessed in clinical trials. These include: