title: How many JAK inhibitors in myelofibrosis?
abstract: The discovery of the activating mutation JAK2 V617F ushered a new era in MPN which included new diagnostic and prognostic criteria as well as a potential therapeutic target. JAK2 inhibition became a reality with first patients receiving drugs that targeted JAK2 in 2007 and was marked by the first approval in 2011 of Ruxolitinib a JAK 1 and 2-inhibitor to treat myelofibrosis (MF). In this article entitled "How many JAK inhibitors for myelofibrosis" we discuss JAK2 as a target, review briefly the benefits to patients with MF of JAK inhibition and highlight some of the differences between the number of JAK inhibitors currently being evaluated. Reflecting upon what we have learnt from the chronic myeloid leukaemia field and for MF regarding disease complexity as well as individual patient factors including resistance we discuss why it is likely we will need several different agents with JAK inhibitory activity. The next chapter discusses combination therapies for myelofibrosis which is a logical step in both trying to cure this disease and improve patient outcome and toxicities with JAK inhibitors.
authors.affiliation: Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London SE1 9RT, UK.
authors.forename: Bruna Velosa
authors.initials: BV
authors.lastname: Ferreira
authors.affiliation: Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London SE1 9RT, UK. Electronic address: Claire@Harrisonlong.co.uk.
authors.forename: Claire
authors.initials: C
authors.lastname: Harrison
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides / Q000627:therapeutic use; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015870:Gene Expression; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D009154:Mutation; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use
chemical_list: C561234:11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001549:Benzamides; D001952:Bridged-Ring Compounds; D056572:Histone Deacetylase Inhibitors; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C546012:N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide; C540383:ruxolitinib; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2
keywords: JAK 1; JAK 2; momelotinib; pacritinib; ruxolitinib