Review
Oncology
Austin P. Runde, Ryan Mack, Peter S. J. Breslin, Jiwang Zhang
Summary: TBK1 is a kinase belonging to the IKK family that can be activated by multiple pathways and involved in various cellular activities. Although TBK1 mutations have not been found in human cancers, aberrant TBK1 activation is associated with the oncogenesis of several types of cancer. Therefore, TBK1 is considered as a feasible target for cancer treatment.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Yi Sun, Or-yam Revach, Seth Anderson, Emily A. A. Kessler, Clara H. H. Wolfe, Anne Jenney, Caitlin E. E. Mills, Emily J. J. Robitschek, Thomas G. R. Davis, Sarah Kim, Amina Fu, Xiang Ma, Jia Gwee, Payal Tiwari, Peter P. P. Du, Princy Sindurakar, Jun Tian, Arnav Mehta, Alexis M. M. Schneider, Keren Yizhak, Moshe Sade-Feldman, Thomas LaSalle, Tatyana Sharova, Hongyan Xie, Shuming Liu, William A. A. Michaud, Rodrigo Saad-Beretta, Kathleen B. B. Yates, Arvin Iracheta-Vellve, Johan K. E. Spetz, Xingping Qin, Kristopher A. A. Sarosiek, Gao Zhang, Jong Wook Kim, Mack Y. Y. Su, Angelina M. M. Cicerchia, Martin Q. Q. Rasmussen, Samuel J. J. Klempner, Dejan Juric, Sara I. I. Pai, David M. M. Miller, Anita Giobbie-Hurder, Jonathan H. H. Chen, Karin Pelka, Dennie T. T. Frederick, Susanna Stinson, Elena Ivanova, Amir R. R. Aref, Cloud P. P. Paweletz, David A. A. Barbie, Debattama R. R. Sen, David E. E. Fisher, Ryan B. B. Corcoran, Nir Hacohen, Peter K. K. Sorger, Keith T. T. Flaherty, Genevieve M. M. Boland, Robert T. T. Manguso, Russell W. W. Jenkins
Summary: In this study, TBK1 was identified as a candidate immune-evasion gene through a genetic screen. Inhibition of TBK1 enhances the response to PD-1 blockade by reducing the cytotoxicity threshold to cytokines. Targeting TBK1 is an effective strategy to overcome resistance to cancer immunotherapy.
Review
Immunology
Min Zhang, Yan Zou, Xujun Zhou, Jinming Zhou
Summary: The cGAS-STING signaling pathway plays a significant role in the host immune response and its abnormal activation is closely related to autoimmune diseases. Targeting this pathway has become a promising strategy for therapy of autoimmune diseases. This review summarizes the key pathways and various autoimmune diseases mediated by the cGAS-STING-TBK1 axis, as well as recent developments in selective inhibitors of cGAS, STING, or TBK1 and their potential application in therapy of cGAS-STING-TBK1 related autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Syn Kok Yeo, Michael Haas, Kanakaraju Manupati, Mingang Hao, Fuchun Yang, Song Chen, Jun-Lin Guan
Summary: This study identified a novel sensitization strategy for breast cancer treatment by activating the TBK-IFN pathway. Disrupting the selective autophagy function was found to activate the AZI2-TBK1-IFN signaling pathway, making breast cancer more responsive to immunotherapy.
Review
Chemistry, Medicinal
Tingting Liu, Shubin Song, Xu Wang, Jifu Hao
Summary: Breast cancer remains a challenging health issue and a top priority in biomedical research. Researchers are increasingly interested in studying breast cancer in young women. Common treatment options for breast cancer include chemotherapy, immunotherapy, hormone therapy, surgery, and radiotherapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Measho H. Abreha, Shamsideen Ojelade, Eric B. Dammer, Zachary T. McEachin, Duc M. Duong, Marla Gearing, Gary J. Bassell, James J. Lah, Allan Levey, Joshua M. Shulman, Nicholas T. Seyfried
Summary: The study identified TBK1 as a tau-interacting partner in Alzheimer's disease and related dementias, with increased TBK1 activation potentially promoting tau hyperphosphorylation and neuronal loss.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Weilian Bao, Xiaohong Liu, Yan You, Hui Hou, Xu Wang, Sulin Zhang, Haidong Li, Guize Feng, Xinyu Cao, Hualiang Jiang, Mingyue Zheng, Xiaoyan Shen
Summary: SNX10 plays a critical role in inflammatory responses in mouse colitis, with its deletion alleviating inflammation by inhibiting TBK1/c-Rel signaling activation. Mechanistically, SNX10 is required for recruiting PIKfyve to TRIF-positive endosomes to regulate LPS-induced inflammation response. The pharmacological inhibitor DC-5X029 targeting SNX10 protein-protein interaction shows potential for treating IBD.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Xiaojing Liang, Ningxia Zhang, Hongming Pan, Jiansheng Xie, Weidong Han
Summary: Store-operated Ca2+ entry (SOCE) is the major pathway of Ca2+ entry in mammalian cells and has been shown to be closely related to cancer development. Developing compounds targeting SOCE is proposed as a potential and effective strategy for cancer therapy.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Baochen Yang, Jing-Quan Wang, Yao Tan, Runzhu Yuan, Zhe-Sheng Chen, Chang Zou
Summary: RNA methylation plays a critical role in various biological processes, including cancer cell proliferation, metastasis, and immune response. RNA methylation-related proteins have become promising targets for cancer therapy.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Medicine, General & Internal
Arvind Dasari, Sara Lonardi, Rocio Garcia-Carbonero, Elena Elez, Takayuki Yoshino, Alberto Sobrero, James Yao, Pilar Garcia-Alfonso, Judit Kocsis, Antonio Cubillo Gracian, Andrea Sartore-Bianchi, Taroh Satoh, Violaine Randrian, Jiri Tomasek, Geoff Chong, Andrew Scott Paulson, Toshiki Masuishi, Jeremy Jones, Tibor Csoszi, Chiara Cremolini, Francois Ghiringhelli, Ardaman Shergill, Howard S. Hochster, John Krauss, Ali Bassam, Michel Ducreux, Anneli Elme, Laurence Faugeras, Stefan Kasper, Eric Van Cutsem, Dirk Arnold, Shivani Nanda, Zhao Yang, William R. Schelman, Marek Kania, Josep Tabernero, Cathy Eng
Summary: This study evaluated the efficacy and safety of fruquintinib, a highly selective and potent oral inhibitor of VEGFRs 1, 2, and 3, in patients with advanced, chemotherapy-refractory colorectal cancer. The results showed that fruquintinib significantly prolonged overall survival compared to placebo in patients with refractory metastatic colorectal cancer, with clinical significance. Therefore, fruquintinib could become a global treatment option for patients with refractory metastatic colorectal cancer.
Article
Medicine, Research & Experimental
Peng Zhao, Xiaoli Sun, Zhongji Liao, Hong Yu, Dan Li, Zeyang Shen, Christopher K. Glass, Joseph L. Witztum, Alan R. Saltiel
Summary: Amlexanox has the potential to improve diet-induced hypertriglyceridemia atherogenesis through synergistic actions involving upregulation of bile acid synthesis, reduction of inflammation, and improvement of vascular dysfunction.
Review
Biochemistry & Molecular Biology
Suryavathi Viswanadhapalli, Kalarickal Dileep, Kam Y. J. Zhang, Hareesh B. Nair, Ratna K. Vadlamudi
Summary: Leukemia inhibitory factor and its receptor are commonly overexpressed in solid cancers, and they have been identified as promising clinical targets for cancer therapy. This signaling pathway plays a key role in tumor growth, metastasis, stemness, therapy resistance, and modulation of immune cells in the tumor microenvironment. Two targeted agents, an anti-LIF antibody and a LIFR inhibitor, have shown effectiveness in preclinical models and are currently being tested in clinical trials.
Article
Oncology
Qinglei Gao, Jianqing Zhu, Weidong Zhao, Yi Huang, Ruifang An, Hong Zheng, Pengpeng Qu, Li Wang, Qi Zhou, Danbo Wang, Ge Lou, Jing Wang, Ke Wang, John Low, Beihua Kong, Abdul Malik Rozita, Lim Chun Sen, Rutie Yin, Xing Xie, Jihong Liu, Wei Sun, Jingya Su, Chunyi Zhang, Rongyu Zang, Ding Ma
Summary: This study evaluated the efficacy and tolerability of olaparib exclusively in Asian patients with platinum-sensitive relapsed ovarian cancer. Results showed that olaparib maintenance therapy was highly effective and well tolerated in this population, regardless of BRCA status.
CLINICAL CANCER RESEARCH
(2022)
Review
Medicine, Research & Experimental
Cheng-Yi Huang, Chih-Ling Chung, Tsung-Hui Hu, Jih-Jung Chen, Pei-Feng Liu, Chun-Lin Chen
Summary: TGF-beta plays crucial roles in cancer by promoting proliferation and metastasis, leading pharmaceutical companies to explore inhibitors for cancer therapy. Despite some setbacks and slow progress, research on TGF-beta signal transduction pathway and inhibitors continues to advance in the field of oncology.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Cell Biology
Jingxuan Chen, Xuemei Wei, Xiao Wang, Tong Liu, Yingchi Zhao, Luoying Chen, Yujie Luo, Hongqiang Du, Yunfei Li, Tongtong Liu, Lili Cao, Zhe Zhou, Zeming Zhang, Ling Liang, Lu Li, Xuhui Yan, Xuehui Zhang, Xuliang Deng, Guang Yang, Ping Yin, Jianlei Hao, Zhinan Yin, Fuping You
Summary: m(6)A modification of mRNA plays a crucial role in antiviral immunity. TBK1 kinase phosphorylates METTL3, a core methyltransferase, and promotes its interaction with the translational complex, enhancing protein translation and antiviral responses. METTL3 also stabilizes IRF3 mRNA and facilitates production of type I interferon. Innate signals activate METTL3 via TBK1, securing antiviral immunity through mRNA stability and protein translation.