Emerging targeted therapies in myelofibrosis

Giovanni Barosi

Research output: Contribution to journalArticlepeer-review

Abstract

Conventional drugs for myelofibrosis are driven by clinical needs, primarily anemia and splenomegaly. With these therapies, stem cell transplantation remains the only potentially curative approach. The discovery that mutations affecting JAK2 or MPL lead to activation of the intracellular JAK-STAT signaling pathway, and that other mutations (TET2, EZH2, ASXL1, IDH1 and IDH2) interfere with the normal machinery of epigenetics, has prompted to the development of therapies targeted at controling the major disease mechanisms. JAK2 ATP competitive inhibitors (ruxolitinib, lestaurtinib, SAR302503, SB1518 and CYT387) or drugs that indirectly inhibit the JAK-STAT pathway (everolimus) have documented major effects on splenomegaly and its constitutional symptoms. Epigenetic drugs (demethylating agents and histone deacetylase inhibitors) have displayed only minor effects on the disease symptoms. Relenting disease progression remains an unmet clinical need.

Original languageEnglish
Pages (from-to)313-324
Number of pages12
JournalExpert Review of Hematology
Volume5
Issue number3
DOIs
Publication statusPublished - Jun 2012

Keywords

  • epigenetic drugs
  • essential thrombocythemia
  • everolimus
  • JAK inhibitors
  • JAK2 V617F
  • lenalidomide
  • myelofibrosis
  • polycythemia vera
  • pomalidomide
  • ruxolitinib
  • stem cell transplantation
  • thalidomide

ASJC Scopus subject areas

  • Hematology

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