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骨髓纤维化中有多少种JAK抑制剂?

How many JAK inhibitors in myelofibrosis?

作者信息

Ferreira Bruna Velosa, Harrison Claire

机构信息

Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London SE1 9RT, UK.

Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London SE1 9RT, UK.

出版信息

Best Pract Res Clin Haematol. 2014 Jun;27(2):187-95. doi: 10.1016/j.beha.2014.07.010. Epub 2014 Jul 18.

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.

摘要

激活突变JAK2 V617F的发现开创了骨髓增殖性肿瘤(MPN)的新纪元,其中包括新的诊断和预后标准以及潜在的治疗靶点。随着首批患者在2007年接受靶向JAK2的药物治疗,JAK2抑制成为现实,并于2011年首次批准鲁索替尼(一种JAK1和JAK2抑制剂)用于治疗骨髓纤维化(MF)。在这篇题为“治疗骨髓纤维化需要多少种JAK抑制剂”的文章中,我们将JAK2作为一个靶点进行讨论,简要回顾JAK抑制对MF患者的益处,并强调目前正在评估的JAK抑制剂数量之间的一些差异。鉴于我们从慢性髓性白血病领域学到的知识以及MF疾病的复杂性和包括耐药性在内的个体患者因素,我们讨论了为何可能需要几种具有JAK抑制活性的不同药物。下一章讨论骨髓纤维化的联合治疗,这是在试图治愈该疾病以及使用JAK抑制剂改善患者预后和毒性方面的合理举措。

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