Janus kinase inhibitors: Jackpot or potluck?
Publication Type:Journal Article
Source:Oncology Reviews, Volume 6, Number 1, p.101-108 (2012)
Keywords:4 pyrimidinediamine, 5 chloro n2 [1 (5 fluoro 2 pyrimidinyl)ethyl] n4 (5 methyl 1h pyrazol 3 yl) 2, abdominal pain, allogeneic stem cell transplantation, anemia, cancer risk, cancer survival, corticosteroid, creatinine blood level, cytopenia, danazol, diarrhea, dizziness, drug approval, drug potency, drug withdrawal, dyspnea, erythropoietin, everolimus, fatigue, fedratinib, food and drug administration, gandotinib, gene mutation, givinostat, histopathology, human, hypotension, Janus kinase 2, Janus kinase inhibitor, lenalidomide, lestaurtinib, molecular cloning, momelotinib, multiple cycle treatment, myeloid metaplasia, myeloproliferative neoplasm, nausea, neutropenia, nonhuman, pacritinib, panobinostat, peripheral neuropathy, placebo, polycythemia vera, pomalidomide, postessential thrombocytopenia, postpolycythemia vera myelofibrosis, prednisolone, priority journal, pruritus, review, ruxolitinib, side effect, signal transduction, splenomegaly, stomatitis, thrombocytopenia, translational research, unclassified drug, vomiting, vorinostat, xl 019
The reports of a unique mutation in the Janus kinase-2 gene (JAK2) in polycythemia vera by several independent groups in 2005 quickly spurred the development of the Janus kinase inhibitors. In one of the great victories of translational research in recent times, the first small-molecule Janus kinase inhibitor ruxolitinib entered a phase I trial in 2007. With the approval of ruxolitinib by the US Federal Drug Administration in November 2011 for high-risk and intermediate-2 risk myelofibrosis, a change in paradigm has occurred in the management of a subset of myeloproliferative neoplasms (MPN): primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Whereas the current evidence for ruxolitinib only covers high-risk and intermediate-2 risk myelofibro-sis, inhibitors with greater potency are likely to offer better disease control and survival advantage in patients belonging to these categories, and possibly to the low-risk and intermediate-1 risk categories of MPN as well. But use of the Janus kinase inhibitors also probably has certain disadvantages, such as toxicity, resistance, withdrawal phenomenon, non-reversal of histology, and an implausible goal of disease clone eradication, some of which could offset the gains. In spite of this, Janus kinase inhibitors are here to stay, and for use in more than just myeloproliferative neoplasms. © Copyright K. Pavithran and S.B. Pande, 2012.
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