The Role and Therapeutic Targeting of JAK/STAT Signaling in Glioblastoma.

The Role and Therapeutic Targeting of JAK/STAT Signaling in Glioblastoma.
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JAK/STAT信号通路在胶质母细胞瘤中的作用和治疗靶点

DOI:
10.3390/cancers13030437
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发表时间:
2021-01-24
期刊:
影响因子:
5.2
通讯作者:
Heimberger AB
Heimberger AB
中科院分区:
医学2区
文献类型:
--
作者:
Ou A;Ott M;Fang D;Heimberger AB

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胶质母细胞瘤是最难治疗的人类恶性肿瘤之一,尽管有一些技术使科学家和临床医生能够更好地了解耐药的分子基础,但在提高胶质母细胞瘤患者的存活率方面进展甚微。我们假设,JAK/STAT信号转导和转录激活因子(JAK/STAT)信号失控代表了肿瘤发生和对药物治疗耐药的一个主要枢纽,其靶向抑制的临床研究是必要的,并强调了从历史研究中吸取的教训。胶质母细胞瘤仍然是最致命和难以治疗的人类恶性肿瘤之一,这在很大程度上是因为它具有弥漫性浸润性、分子异质性和免疫逃逸能力。Janus激酶/信号转导和转录激活因子(JAK/STAT)信号通路在多种促肿瘤功能中起重要作用,包括增殖、抗凋亡、血管生成、干细胞维持和免疫抑制。我们回顾了关于JAK/STAT信号在胶质母细胞瘤中的生物学作用、治疗策略和该领域未来发展方向的知识现状。
Glioblastoma is one of the most treatment-refractory human malignancies, and despite techniques that have allowed scientists and clinicians to better understand the molecular underpinnings of resistance, little progress has been made in improving the survival of patients with glioblastoma. We posit that dysregulated Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling represents one major hub of tumorigenesis and resistance to medical therapies and that clinical study of its targeted inhibition is warranted, as well as highlighting the lessons learned from historical investigation going forward. Glioblastoma remains one of the deadliest and treatment-refractory human malignancies in large part due to its diffusely infiltrative nature, molecular heterogeneity, and capacity for immune escape. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes substantively to a wide variety of protumorigenic functions, including proliferation, anti-apoptosis, angiogenesis, stem cell maintenance, and immune suppression. We review the current state of knowledge regarding the biological role of JAK/STAT signaling in glioblastoma, therapeutic strategies, and future directions for the field.
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