Janus kinase inhibitors

An update on the progress and promise of targeted therapy in the myeloproliferative neoplasms

Brady L. Stein, John D. Crispino, Alison R Moliterno

Research output: Contribution to journalArticle

Abstract

Purpose of Review: The discovery of the JAK2 V617F mutation in the classical myeloproliferative neoplasms (MPNs) essential thrombocytosis, polycythemia vera, and primary myelofibrosis has ushered in a new era of scientific discovery in these diseases, resulting in a molecular classification and an improved understanding of disease pathogenesis. Alongside this period of discovery has been the rapid development of targeted therapy and, here, we summarize results from clinical trials involving these small molecule Janus family of tyrosine kinase (JAK) inhibitors. Recent Findings: The JAK inhibitors consistently alleviate constitutional symptoms and reduce spleen size. Early phase testing indicates that some of these inhibitors have additional unique effects: INCB018424 results in a significant reduction in the level of pro-inflammatory cytokines; TG101348 may modify disease burden as assessed by JAK2 allele measurements; and CYT387 ameliorates anemia. Summary: The initial enthusiasm for these agents has been tempered by recognition that JAK2 V617F may represent only one component of lesions driving the heterogeneity of the MPN. Clinical trial design cannot address important disease endpoints such as thrombosis or leukemia transformation, but it appears that JAK inhibitors will offer an important palliative option and because of the molecular complexity in these diseases, it might be rational to give these inhibitors along with other agents that target alternate mechanisms of the disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)609-616
Number of pages8
JournalCurrent Opinion in Oncology
Volume23
Issue number6
DOIs
StatePublished - Nov 2011

Fingerprint

Janus Kinases
Neoplasms
Therapeutics
Clinical Trials
Thrombocytosis
Polycythemia Vera
Primary Myelofibrosis
Protein-Tyrosine Kinases
Anemia
Leukemia
Thrombosis
Spleen
Alleles
Cytokines
Mutation

Keywords

  • Janus family of tyrosine kinase inhibitors
  • myeloproliferative neoplasms
  • targeted therapies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Janus kinase inhibitors : An update on the progress and promise of targeted therapy in the myeloproliferative neoplasms. / Stein, Brady L.; Crispino, John D.; Moliterno, Alison R.

In: Current Opinion in Oncology, Vol. 23, No. 6, 11.2011, p. 609-616.

Research output: Contribution to journalArticle

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