JAK2 inhibitors: are they the solution?
JAK2 inhibitors: are they the solution?
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DOI：
10.1016/j.clml.2011.02.007
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Verstovsek S
中科院分区：
文献类型：
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作者：
Santos FP;Verstovsek S
费城阴性骨髓增生性肿瘤（Ph 阴性 MPN）患者中 JAK2V617F 突变的发现开启了这些疾病的靶向治疗时代。到目前为止，患者可用的治疗选择很少，通常仅限于羟基脲、干扰素制剂和更具侵袭性的病例的化疗。 JAK2抑制剂的研发经过了5年的时间，最近发表了首个JAK2抑制剂治疗骨髓纤维化患者的临床试验结果。目前的结果表明，JAK2抑制剂有可能减轻疾病负担及其活性，具体表现为脾肿大的减少和全身疾病相关症状的改善，但它们似乎无法根除恶性克隆。另一方面，JAK2抑制剂可以帮助患者，无论其突变状态如何，因为没有JAK2V617F突变的患者与有JAK2V617F突变的患者受益程度相同。在我们用药物治疗治愈骨髓纤维化之前，需要更好地了解 MPN 的病理生理学。目前，几种新型JAK2抑制剂正在针对MF患者进行临床试验，针对PV和ET患者的临床试验也已启动。我们回顾了 JAK2 抑制剂用于治疗 Ph 阴性 MPN 患者的最新数据。
The discovery of the JAK2V617F mutation in patients with Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) started the era of targeted therapy for these diseases. Until now, patients had few treatment options available, usually restricted to hydroxyurea, interferon preparations, and chemotherapy in more aggressive cases. JAK2 inhibitors have been developed over the past 5 years, and the results of the first clinical trials with JAK2 inhibitors for patients with myelofibrosis were recently published. Current results suggest that JAK2 inhibitors have a potential to decrease disease burden and its activity, as manifested by a decrease in splenomegaly and improvement in systemic disease-related symptoms, but they do not seem to be able to eradicate the malignant clone. On the other hand, JAK2 inhibitors help patients regardless of their mutation status as patients without JAK2V617F mutation benefit to the same extent as patients with JAK2V617F mutation. A greater understanding of the pathophysiology of MPNs is needed before we can cure myelofibrosis with drug therapy. Currently, several new JAK2 inhibitors are in clinical trials for patients with MF and clinical trials for patients with PV and ET have also started. We review recent data on JAK2 inhibitors for the management of patients with Ph-negative MPNs.