Targeting TANK-binding kinase 1 (TBK1) in cancer.
Targeting TANK-binding kinase 1 (TBK1) in cancer.
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靶向坦克结合激酶1 （TBK1）在癌症中的作用。
DOI：
10.1080/14728222.2020.1826929
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发表时间：
2020-11
影响因子：
5.8
通讯作者：
Jenkins RW
中科院分区：
文献类型：
--
作者：
Revach OY;Liu S;Jenkins RW
TANK-binding kinase 1 （TBK1）是一种丝氨酸/苏氨酸激酶，在协调细胞对入侵病原体的反应和调节关键的炎症信号级联反应中起中心作用。虽然完整的TBK1信号传导是成功的抗病毒信号传导所必需的，但TBK1信号传导失调与多种病理生理状况有关，包括癌症。一些证据支持TBK1在癌症发病机制中的作用，但TBK1的具体作用和调控仍不完全清楚。一个关键的挑战是由TBK1调节的细胞过程的多样性，包括炎症、细胞周期、自噬、能量稳态和细胞死亡。然而，来自临床前癌症模型的证据表明，靶向TBK1可能是特定环境下抗癌治疗的有效策略。本文综述了TBK1的作用和调控，重点介绍了TBK1的癌症发病机制和作为抗癌策略的药物靶向。相关文献来源于PubMed检索，包括1999年至2020年的研究。TBK1正在成为抗癌治疗的潜在靶点。单独抑制TBK1可能不足以抑制大多数癌症的生长，因此可能需要联合策略。提高对肿瘤内生性和肿瘤外源性TBK1信号的理解将为新的治疗策略提供信息。
TANK-binding kinase 1 (TBK1) is a Ser/Thr kinase with a central role in coordinating the cellular response to invading pathogens and regulating key inflammatory signaling cascades. While intact TBK1 signaling is required for successful anti-viral signaling, dysregulated TBK1 signaling has been linked to a variety of pathophysiologic conditions, including cancer. Several lines of evidence support a role for TBK1 in cancer pathogenesis, but the specific roles and regulation of TBK1 remain incompletely understood. A key challenge is the diversity of cellular processes that are regulated by TBK1, including inflammation, cell cycle, autophagy, energy homeostasis, and cell death. Nevertheless, evidence from pre-clinical cancer models suggest that targeting TBK1 may be an effective strategy for anti-cancer therapy in specific settings. This review provides an overview of the roles and regulation of TBK1 with a focus on cancer pathogenesis and drug targeting of TBK1 as an anti-cancer strategy. Relevant literature was derived from a PubMed search encompassing studies from 1999 to 2020. TBK1 is emerging as a potential target for anti-cancer therapy. Inhibition of TBK1 alone may be insufficient to restrain the growth of most cancers, hence combination strategies will likely be necessary. Improved understanding of tumor-intrinsic and tumor-extrinsic TBK1 signaling will inform novel therapeutic strategies.
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