文章：

Janus激酶/信号转导与转录激活因子通路在皮肤T细胞淋巴瘤中的治疗靶向研究

Therapeutic Targeting of the Janus Kinase/Signal Transducer and Activator of Transcription Pathway in Cutaneous T-Cell Lymphoma

原文发布日期：7 February 2025

DOI: 10.3390/cancers17040568

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: Cutaneous T-cell lymphoma (CTCL) is a rare group of non-Hodgkin lymphomas characterized by the clonal expansion of malignant T cells. While current treatments can alleviate symptoms and significant progress has been made in treating leukemic CTCL, a definitive cure remains elusive. Dysregulation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is a key driver of CTCL pathogenesis. As a result, therapeutic strategies targeting JAK/STAT signaling have gained momentum, with the increasing use of JAK inhibitors and other agents that effectively suppress this pathway. These immune-modulating therapies have broad effects on physiological processes, inflammation, and the pathological changes associated with both inflammatory diseases and cancers. Several JAK inhibitors, originally FDA-approved for inflammatory conditions, are now being investigated for cancer treatment.Methods: In this paper, a brief review of the literature on JAK/STAT pathway dysregulation in CTCL is provided, highlighting both clinical and preclinical studies involving JAK inhibitors and other agents that target this pathway.Results: Specifically, we focus on six JAK inhibitors currently under clinical investigation—golidocitinib, ruxolitinib, cerdulatinib, tofacitinib, upadacitinib, and abrocitinib. Additionally, we discuss preclinical studies that explore the mechanisms underlying JAK/STAT pathway inhibition in CTCL. Furthermore, we review reported cases in which CTCL relapsed or emerged following JAK inhibitor treatment.Conclusions: Collectively, these findings support the potential clinical utility of targeting the JAK/STAT pathway in CTCL. However, further research is needed to evaluate safety risks, minimize adverse effects, and optimize these therapeutic strategies.

摘要翻译： 

背景/目的：皮肤T细胞淋巴瘤（CTCL）是一组罕见的非霍奇金淋巴瘤，其特征为恶性T细胞的克隆性扩增。尽管现有治疗可缓解症状，且在治疗白血病性CTCL方面已取得显著进展，但彻底治愈仍难以实现。Janus激酶/信号转导与转录激活因子（JAK/STAT）信号通路的失调是CTCL发病机制的关键驱动因素。因此，靶向JAK/STAT信号通路的治疗策略日益受到重视，JAK抑制剂及其他有效抑制该通路的药物应用逐渐增多。这些免疫调节疗法对生理过程、炎症反应以及与炎性疾病和癌症相关的病理改变具有广泛影响。数种最初获美国FDA批准用于炎症性疾病的JAK抑制剂，现正被探索用于癌症治疗。 方法：本文简要综述了关于CTCL中JAK/STAT通路失调的文献，重点介绍了涉及JAK抑制剂及其他靶向该通路药物的临床与临床前研究。 结果：我们特别聚焦于目前处于临床研究阶段的六种JAK抑制剂——戈利多替尼、鲁索替尼、塞度替尼、托法替尼、乌帕替尼和阿布昔替尼。此外，我们还探讨了临床前研究中关于JAK/STAT通路在CTCL中抑制机制的研究，并综述了已报道的CTCL在JAK抑制剂治疗后复发或新发病例。 结论：总体而言，这些发现支持了靶向JAK/STAT通路在CTCL治疗中的潜在临床应用价值。然而，仍需进一步研究以评估安全风险、减少不良反应并优化这些治疗策略。

原文链接：

Therapeutic Targeting of the Janus Kinase/Signal Transducer and Activator of Transcription Pathway in Cutaneous T-Cell Lymphoma