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|Ref Type||Journal Article|
|Authors||Mascarenhas J, Hoffman R|
|Title||Ruxolitinib: the first FDA approved therapy for the treatment of myelofibrosis.|
|Journal||Clinical cancer research : an official journal of the American Association for|
|Date||2012 Jun 1|
|Abstract Text||The BCR-ABL1-negative myeloproliferative neoplasms (e.g., essential thrombocythemia, polycythemia vera, and primary myelofibrosis) are a group of heterogeneous hematologic malignancies that involve a clonal proliferation of hematopoietic stem cells. Thrombosis, bleeding, and transformation to acute leukemia reduce the overall survival of patients with myelofibrosis, a disease typified by progressive splenomegaly and disease-related symptoms such as fatigue, pruritus, and bony pains. Hematopoietic stem cell transplant offers the only potential for cure in a minority of eligible patients, leaving a serious unmet need for improved therapies. Recent advances in our understanding of the pathogenetic mechanisms underlying these diseases have led to an explosion of clinical trials evaluating novel therapies. The discovery of an activating mutation in the Janus-activated kinase 2 (JAK2) gene provided a therapeutic target to downregulate this activated signaling pathway, which influences the phenotype of these diseases. Ruxolitinib (Jakafi; Incyte) is a small-molecule inhibitor of JAK1/2 that has proved to be effective at reducing splenomegaly and ameliorating symptoms in myeloproliferative neoplasms. Based on the results of 2 pivotal randomized phase III clinical trials, ruxolitinib has become the first therapeutic to be approved by the U.S. Food and Drug Administration for treatment of patients with myelofibrosis. Ruxolitinib offers a well-tolerated oral therapeutic option for patients with myelofibrosis with symptomatic splenomegaly and debilitating disease-related symptoms, but it does not seem to be effective at eliminating the underlying hematological malignancy.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Ruxolitinib||Jakafi||INCB 18424|INCB018424|INCB18424||JAK1 Inhibitor - ATP competitive 4 JAK2 Inhibitor - ATP competitive 14||Jakafi (ruxolitinib) is an inhibitor of protein tyrosine kinases JAK1 and JAK2, thus resulting in reduced inflammation and reduced proliferation (PMID: 22474318). Jakafi (ruxolitinib) is FDA approved to treat bone marrow cancer, specifically intermediate or high-risk myelofibrosis (FDA.gov)|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||myelofibrosis||not applicable||Ruxolitinib||FDA approved||Actionable||In a Phase III clinical trial that supported FDA approval, treatment with Jakafi (ruxolitinib) resulted in a decrease in spleen volume of greater than or equal to 35% in 41.9% of patients with intermediate or high-risk myelofibrosis, compared to 0.7% of patients treated with the placebo (PMID: 22474318).||detail... 22474318|