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What is next beyond janus kinase 2 inhibitors for primary myelofibrosis?
MedLine Citation:
PMID:  23385614     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: Although the approval of the janus kinase (JAK) inhibitor ruxolitinib for therapy of patients with myelofibrosis represents an important step in the development of targeted therapy for these patients, JAK inhibitors do not eradicate the disease, and a review of novel agents with mechanisms of action complementary to JAK2 enzymatic inhibition is timely.
RECENT FINDINGS: There are several compounds with different mechanisms of action undergoing preclinical and clinical testing in myelofibrosis. Heat shock protein inhibitors and histone deacetylase inhibitors induce JAK2 degradation and downregulation of intracellular oncogenic signalling, and may overcome resistance to JAK2 inhibitors. Reversal of bone marrow fibrosis is still a therapeutic challenge in this disease, and mAbs targeting transforming growth factor-β and lysyl oxidase like-2 may prove efficacious. Promising compounds inhibiting signal transducer and activator of transcription 5 activity and inducing megakaryocyte polyploidization are in preclinical testing.
SUMMARY: Although none of these new drugs have been approved for therapy of myelofibrosis, their activity is being tested in clinical trials, alone or in combination with JAK2 inhibitors. Patients with myelofibrosis should be encouraged to participate in clinical trials testing novel compounds for this disorder, particularly if they have failed a trial of JAK2 inhibitors.
Authors:
Fabio P S Santos; Srdan Verstovsek
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Current opinion in hematology     Volume:  20     ISSN:  1531-7048     ISO Abbreviation:  Curr. Opin. Hematol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9430802     Medline TA:  Curr Opin Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  123-9     Citation Subset:  IM    
Affiliation:
aHematology and Oncology Institute, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil bDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
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