Novel agents for the treatment of polycythemia vera: an insight into preclinical research and early phase clinical trials.
Novel agents for the treatment of polycythemia vera: an insight into preclinical research and early phase clinical trials.
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DOI：
10.1080/13543784.2020.1782886
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发表时间：
2020-08
影响因子：
6.1
通讯作者：
Mesa R
中科院分区：
文献类型：
--
作者：
Padrnos L;Mesa R
目前对真性红细胞增多症 (PV) 的治疗有限，主要针对血栓形成风险。针对骨髓增殖中不同作用机制的药物正在进行临床评估，以优化疗效、提高耐受性并增加长期疾病并发症。本文回顾了已完成的 PV 早期临床试验的当前数据，无论是作为单一疗法还是与目前批准的少数药物联合使用。 PV 管理仍然有机会提高疗效并降低疾病进展的风险。使用长效干扰素的不断变化的数据有助于阐明这种疗法的潜在一线作用。 JAK2 抑制对降低羟基脲耐药/难治性疾病患者的发病率产生了重大影响。新方法可能很快会扩大选择范围，包括组蛋白脱乙酰酶抑制剂（HDACi），无论是单一疗法还是联合疗法，都显示出有希望的活性和对瘙痒的症状控制。针对新分子途径（雷帕霉素的哺乳动物靶标、胰岛素受体底物 1/2、MDM2 蛋白）或铁代谢途径的药物正处于早期试验阶段。评估疗效、长期并发症、生存率和全身症状控制的进一步转化研究可能为未来 PV 药物开发的成功铺平道路，无论是单一疗法还是联合疗法。
Current treatment for polycythemia vera (PV) is limited and primarily targets thrombosis risk. Agents targeting distinct mechanisms of action within myeloproliferation are undergoing clinical evaluation to optimize efficacy, improve tolerance and augment long term disease complications. This article reviews the current data from completed early phase clinical trials in PV, either as monotherapy or in combination with the few currently approved agents. There remains an opportunity in PV management to improve efficacy and decrease risk of disease progression. Evolving data from use of long acting interferons are serving to clarifying the potential front line role of this therapy. JAK2 inhibition has made a significant impact on decreasing morbidity in patients with hydroxyurea resistant/refractory disease. New approaches may soon expand options including histone deactylase inhibitors (HDACi), either as monotherapy or combination therapy, which showed promising activity and symptomatic control of pruritus. Drugs targeting new molecular pathways (mammalian target of rapamycin, insulin receptor substrates 1/2, MDM2 protein) or the iron metabolism pathway are in early phase trial. Further translational studies assessing efficacy, long term complications, survival, and constitutional symptom control could pave a way for future success in PV drug development either as monotherapy or in combination.
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影响因子：
45.3
作者：
Emanuel, Robyn M.;Dueck, Amylou C.;Mesa, Ruben A.
通讯作者：
Mesa, Ruben A.
影响因子：
20.3
作者：
Finazzi, G;Caruso, V;Barbui, T
通讯作者：
Barbui, T
影响因子：
24.7
作者：
Gisslinger, Heinz;Klade, Christoph;Kiladjian, Jean-Jacques
通讯作者：
Kiladjian, Jean-Jacques
影响因子：
15.9
作者：
Guo, Shuling;Casu, Carla;Rivella, Stefano
通讯作者：
Rivella, Stefano
DOI：
10.1016/j.clml.2013.07.011
发表时间：
2013-09-01
期刊：
Clinical lymphoma, myeloma & leukemia
影响因子：
--
作者：
Bartalucci, Niccolo;Guglielmelli, Paola;Vannucchi, Alessandro M
通讯作者：
Vannucchi, Alessandro M