Targeting TANK-binding kinase 1 (TBK1) in cancer
Or-Yam Revach1,2, Shuming Liu2, Russell W Jenkins1,2
1Massachusetts General Hospital Cancer Center, Harvard Medical School , Boston, MA, USA.
Introduction:
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 suggests that targeting TBK1 may be an effective strategy for anti-cancer therapy in specific settings.
Areas Covered:
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.
Expert Opinion:
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.
Insights
TANK-binding kinase 1 (TBK1) plays a role in cancer. Targeting TBK1 shows promise for anti-cancer therapy, likely requiring combination strategies for effectiveness.
Area of Science:
- Molecular Biology
- Oncology
- Immunology
Background:
- TANK-binding kinase 1 (TBK1) regulates inflammatory signaling and cellular responses to pathogens.
- Dysregulated TBK1 signaling is implicated in various diseases, including cancer.
- TBK1 influences diverse cellular processes such as inflammation, cell cycle, autophagy, and cell death.
Purpose of the Study:
- To review the roles and regulation of TBK1 in cancer pathogenesis.
- To discuss TBK1 as a drug target for anti-cancer strategies.
- To explore potential therapeutic approaches involving TBK1 inhibition.
Main Methods:
- Literature review of studies from 1999 to 2020.
- PubMed database search for relevant research.
- Synthesis of findings on TBK1's role in cancer.
Main Results:
- TBK1 is involved in cancer development and progression.
- Pre-clinical models suggest TBK1 targeting as a potential anti-cancer therapy.
- Inhibition of TBK1 alone may not be sufficient for cancer treatment.
Conclusions:
- TBK1 is an emerging target for anti-cancer therapies.
- Combination strategies involving TBK1 inhibition are likely necessary.
- Further understanding of TBK1 signaling in tumors will guide novel therapeutic development.
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