Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, 1500 E Duarte Road, Duarte, CA, 91010, USA.
Curr Hematol Malig Rep. 2019 Dec;14(6):570-576. doi: 10.1007/s11899-019-00545-5.
T cell lymphoproliferative disorders represent a diverse group of hematologic malignancies with poor prognosis underscoring the need for novel therapeutic approaches. Disruption of the JAK/STAT signaling pathway has been described in this group of blood cancers and may represent an approach for targeted therapy. Here, we summarize the current data describing the disruptions of JAK/STAT signaling in T cell malignancies and focus on the existing evidence for exploitation of this pathway with targeted therapies.
To date, preclinical studies have demonstrated the efficacy of JAK/STAT inhibition in the treatment of several T cell lymphoproliferative disorders. More recently, several early clinical trials have demonstrated promising results utilizing this approach as well. The benefit of the combination of JAK/STAT-targeted therapies along with immunotherapy and other molecularly targeted therapies is also discussed. There is substantial evidence that targeting the JAK/STAT pathway in T cell lymphoproliferative disorders could be of clinical benefit. There are several early clinical trials showing promise and many ongoing trials investigating the optimal utility of agents that inhibit this signaling pathway. In addition, targeting this pathway may provide a platform for further rational combination therapies.
目的综述:T 细胞淋巴增生性疾病是一组预后不良的血液恶性肿瘤,这突显了需要新的治疗方法。在这群血液癌症中已描述了 JAK/STAT 信号通路的破坏,这可能代表了靶向治疗的一种方法。在这里,我们总结了描述 T 细胞恶性肿瘤中 JAK/STAT 信号通路破坏的现有数据,并重点介绍了利用靶向治疗来利用该途径的现有证据。
最新发现:迄今为止,临床前研究已经证明了 JAK/STAT 抑制在治疗几种 T 细胞淋巴增生性疾病中的疗效。最近,几项早期临床试验也证明了这种方法的有效性。还讨论了 JAK/STAT 靶向治疗与免疫疗法和其他分子靶向疗法联合应用的益处。有大量证据表明,针对 T 细胞淋巴增生性疾病中的 JAK/STAT 通路可能具有临床益处。有几项早期临床试验显示出希望,并且许多正在进行的试验正在研究抑制这种信号通路的药物的最佳用途。此外,靶向该途径可能为进一步的合理联合治疗提供平台。