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JAK 抑制剂治疗骨髓纤维化:优势与局限。

JAK Inhibitors for Myelofibrosis: Strengths and Limitations.

机构信息

Department of Haematology, Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK.

出版信息

Curr Hematol Malig Rep. 2024 Dec;19(6):264-275. doi: 10.1007/s11899-024-00744-9. Epub 2024 Oct 14.

Abstract

PURPOSE OF REVIEW

The landscape of myelofibrosis (MF) has changed since the discovery of the JAK2 V617F mutation and subsequent development of JAK inhibitors (JAKis). However, treatment with JAKis remain a challenge. In this review we critically analyze the strengths and limitations of currently available JAK inhibitors.

RECENT FINDINGS

In MF patients, JAK inhibitors have been associated with reduced symptom burden and spleen size, as well as improved survival. However, durability of response and development of treatment resistance remain an issue. Recently, there has been increased efforts to optimize treatment with the development of highly selective JAK inhibitors, as well as use of combination agents to counter disease resistance through targeting aberrant signaling pathways. Treatment of MF patients with JAKi therapy can be challenging but the development of more potent and selective JAK inhibitors, as well as combination therapies, represent exciting treatment advances in this field.

摘要

目的综述

自发现 JAK2 V617F 突变和随后开发 JAK 抑制剂(JAKi)以来,骨髓纤维化(MF)的治疗格局发生了变化。然而,JAKi 的治疗仍然是一个挑战。在这篇综述中,我们批判性地分析了目前可用的 JAK 抑制剂的优缺点。

最近的发现

在 MF 患者中,JAK 抑制剂与减轻症状负担和脾脏大小以及改善生存有关。然而,反应的持久性和治疗耐药性的发展仍然是一个问题。最近,人们越来越努力地通过开发高度选择性的 JAK 抑制剂以及使用联合药物通过靶向异常信号通路来对抗疾病耐药性来优化治疗。用 JAKi 治疗 MF 患者具有挑战性,但更有效和选择性的 JAK 抑制剂的开发以及联合治疗代表了该领域令人兴奋的治疗进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e41/11567979/2271319227c3/11899_2024_744_Fig1_HTML.jpg

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