TY - JOUR
T1 - A potential role of ruxolitinib in leukemia
AU - Naqvi, Kiran
AU - Verstovsek, Srdan
AU - Kantarjian, Hagop
AU - Ravandi, Farhad
N1 - Funding Information:
F Ravandi has received research funding from Incyte and honoraria from Novartis. S Verstovsek has received research funding from Incyte. H Kantarjian has research funding from Novartis. K Naqvi has nothing to disclose.
PY - 2011/8
Y1 - 2011/8
N2 - Introduction: An increased understanding of cellular signaling pathways, like the JAKSTAT pathway, and the identification of the JAK2 V617F mutation in the classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), has generated great interest in the development of targeted JAK2 inhibitors. In a recently completed Phase III study, ruxolitinib, a selective orally available JAK1 and JAK2 inhibitor, has shown efficacy in patients with advanced myelofibrosis. Constitutive activation of the JAKSTAT pathway has also been implicated in other hematological malignancies suggesting a potential role of JAK kinase inhibitors in these malignancies. Areas covered: This article reviews the chemistry, pharmacodynamics, pharmacokinetics, clinical efficacy, safety and tolerability of ruxolitinib. The literature for this article was retrieved from PubMed database searches using the keywords 'ruxolitinib', 'INCB 018424', 'JAK2 inhibitors' and 'leukemia'. Expert opinion: The JAKSTAT signaling pathway plays a vital role in leukemogenesis. Ruxolitinib, a potent JAK1 and JAK2 inhibitor, known to decrease spleen size and alleviate constitutional symptoms in myelofibrosis, represents a potentially promising agent for the treatment of leukemias by inhibiting the JAKSTAT signaling. Further studies of ruxolitinib, in patients with acute and chronic leukemias, are now needed to establish the clinical usefulness of this promising drug.
AB - Introduction: An increased understanding of cellular signaling pathways, like the JAKSTAT pathway, and the identification of the JAK2 V617F mutation in the classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), has generated great interest in the development of targeted JAK2 inhibitors. In a recently completed Phase III study, ruxolitinib, a selective orally available JAK1 and JAK2 inhibitor, has shown efficacy in patients with advanced myelofibrosis. Constitutive activation of the JAKSTAT pathway has also been implicated in other hematological malignancies suggesting a potential role of JAK kinase inhibitors in these malignancies. Areas covered: This article reviews the chemistry, pharmacodynamics, pharmacokinetics, clinical efficacy, safety and tolerability of ruxolitinib. The literature for this article was retrieved from PubMed database searches using the keywords 'ruxolitinib', 'INCB 018424', 'JAK2 inhibitors' and 'leukemia'. Expert opinion: The JAKSTAT signaling pathway plays a vital role in leukemogenesis. Ruxolitinib, a potent JAK1 and JAK2 inhibitor, known to decrease spleen size and alleviate constitutional symptoms in myelofibrosis, represents a potentially promising agent for the treatment of leukemias by inhibiting the JAKSTAT signaling. Further studies of ruxolitinib, in patients with acute and chronic leukemias, are now needed to establish the clinical usefulness of this promising drug.
KW - INCB 018424
KW - JAK2 inhibitors
KW - Leukemia
KW - Ruxolitinib
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UR - http://www.scopus.com/inward/citedby.url?scp=79960353150&partnerID=8YFLogxK
U2 - 10.1517/13543784.2011.589383
DO - 10.1517/13543784.2011.589383
M3 - Review article
C2 - 21635221
AN - SCOPUS:79960353150
SN - 1354-3784
VL - 20
SP - 1159
EP - 1166
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 8
ER -