The Development and Use of Janus Kinase 2 Inhibitors for the Treatment of Myeloproliferative Neoplasms

Following the discovery of the JAK2V617F mutation, Janus kinase (JAK) 2 inhibitors were developed as rationally designed therapy in myeloproliferative neoplasms (MPNs). Although JAK2 inhibitors have clinical efficacy in MPN, they are not clonally selective for the JAK2V617F-mutant cells. Because act...

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Bibliographic Details
Published inHematology/oncology clinics of North America Vol. 31; no. 4; p. 613
Main Authors Hobbs, Gabriela S, Rozelle, Sarah, Mullally, Ann
Format Journal Article
LanguageEnglish
Published United States 01.08.2017
Subjects
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Clinical Trials as Topic
Drug Evaluation, Preclinical
Humans
Janus Kinase 2 - antagonists & inhibitors
Janus Kinase 2 - chemistry
Janus Kinase 2 - genetics
Janus Kinase 2 - metabolism
Molecular Targeted Therapy
Mutation
Myeloproliferative Disorders - drug therapy
Myeloproliferative Disorders - genetics
Myeloproliferative Disorders - metabolism
Polycythemia Vera - drug therapy
Polycythemia Vera - genetics
Polycythemia Vera - metabolism
Primary Myelofibrosis - drug therapy
Primary Myelofibrosis - genetics
Primary Myelofibrosis - metabolism
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Signal Transduction - drug effects
STAT Transcription Factors - metabolism
Treatment Outcome
JAK2V617F mutation
Myelofibrosis
Myeloproliferative neoplasms
JAK-STAT signaling
Polycythemia vera
JAK2 inhibitors
Mutant calreticulin
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Summary:Following the discovery of the JAK2V617F mutation, Janus kinase (JAK) 2 inhibitors were developed as rationally designed therapy in myeloproliferative neoplasms (MPNs). Although JAK2 inhibitors have clinical efficacy in MPN, they are not clonally selective for the JAK2V617F-mutant cells. Because activated JAK-signal transducer and activator of transcription (STAT) signaling is a common feature of MPN, JAK2 inhibitors are efficacious regardless of the specific MPN phenotypic driver mutation. The Food and Drug Administration approved the JAK1/JAK2 inhibitor, ruxolitinib, for the treatment of myelofibrosis and polycythemia vera. Additional JAK2 inhibitors are currently in advanced phased clinical trials.
ISSN:1558-1977
DOI:10.1016/j.hoc.2017.04.002