Document Detail


Emerging drugs for myelofibrosis.
MedLine Citation:
PMID:  23186315     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: Myelofibrosis (MF), a Philadelphia chromosome-negative myeloproliferative neoplasm, is a life-threatening heterogeneous disorder characterized by dysregulation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling network. The clinical hallmarks of MF are progressive splenomegaly, anemia and debilitating symptoms attributable to ineffective hematopoiesis and excessive production of proinflammatory cytokines.
AREAS COVERED: This review describes the pathogenesis, clinical features and current treatment of MF, clinical data for ruxolitinib, a potent oral JAK1/JAK2 inhibitor and the only therapy approved for the treatment of MF, and agents in development for the treatment of MF. Information was derived from relevant MF articles identified in the published literature and abstracts of recent congresses.
EXPERT OPINION: Ruxolitinib reduces spleen size and alleviates MF-related symptoms, thereby improving quality of life. Ruxolitinib may increase the risk of anemia and thrombocytopenia and does not appear to reverse bone marrow fibrosis. Studies are exploring ruxolitinib dosing strategies for patients with low platelet counts and combination therapies. Several other JAK inhibitors and other agents (i.e., immunomodulators, antifibrotic agents, anti-anemia agents, mammalian target of rapamycin [mTOR] inhibitors, epigenetic modifiers, pegylated interferon-α2a) to treat various aspects of MF (i.e., to improve blood counts or forestall marrow fibrosis) are in early clinical development.
Authors:
Ehab Atallah; Srdan Verstovsek
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Expert opinion on emerging drugs     Volume:  17     ISSN:  1744-7623     ISO Abbreviation:  Expert Opin Emerg Drugs     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-28     Completed Date:  2013-05-01     Revised Date:  2014-06-13    
Medline Journal Info:
Nlm Unique ID:  101135662     Medline TA:  Expert Opin Emerg Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  555-70     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Anemia / drug therapy,  etiology
Animals
Cytokines / metabolism
Drug Design*
Hematopoiesis
Humans
Janus Kinase 1 / antagonists & inhibitors
Janus Kinase 2 / antagonists & inhibitors
Primary Myelofibrosis / drug therapy*,  physiopathology
Pyrazoles / therapeutic use*
Quality of Life
Splenomegaly / drug therapy,  etiology
Grant Support
ID/Acronym/Agency:
P30 CA016672/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 0/INCB018424; 0/Pyrazoles; EC 2.7.010.2/JAK1 protein, human; EC 2.7.10.2/JAK2 protein, human; EC 2.7.10.2/Janus Kinase 1; EC 2.7.10.2/Janus Kinase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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