Review
Biochemistry & Molecular Biology
Andrea Spallarossa, Bruno Tasso, Eleonora Russo, Carla Villa, Chiara Brullo
Summary: This review focuses on compounds that can block Focal adhesion kinase (FAK) with different potencies and mechanisms of action, as well as the emergence of new PROTAC molecules. It provides important insights into new FAK inhibitors and offers information for future investigations, particularly from a medicinal chemistry perspective.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Pengcheng Lv, Kun Chen, Hai-Liang Zhu
Summary: FAK, a non-receptor tyrosine kinase, has emerged as a potential therapeutic target for human metastatic cancers due to its overexpression. Recent progress in small molecule FAK inhibitors includes the development of type I, II, and III inhibitors, as well as inhibitors targeting FAK using protein-protein interactions. Insights and perspectives on the future development of FAK inhibitors as anticancer therapeutics have also been provided.
CURRENT MEDICINAL CHEMISTRY
(2021)
Review
Medicine, Research & Experimental
Xianbo Wu, Jie Wang, Qi Liang, Rongsheng Tong, Jianli Huang, Xinwei Yang, Yihua Xu, Wenjing Wang, Minghan Sun, Jianyou Shi
Summary: FAK is an important target for cancer treatment, and many small molecule inhibitors have shown efficacy in inhibiting tumor growth and metastasis. Dual inhibitors that block FAK and other factors simultaneously can improve therapeutic efficacy and overcome drug resistance.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Chiara Brullo, Bruno Tasso
Summary: Focal adhesion kinase (Fak) is a cytoplasmic protein tyrosine kinase that is overexpressed and activated in various solid cancers, playing a significant role in metastasis, cell migration, invasion, and angiogenesis. Research is focusing on developing new, more active and selective Fak inhibitors as potential anti-cancer drugs. Currently, only a few reversible ATP-competitive inhibitors are in pre-clinical studies and clinical trials.
CURRENT MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Xiao-Jing Pang, Xiu-Juan Liu, Yuan Liu, Wen-Bo Liu, Yin-Ru Li, Guang-Xi Yu, Xin-Yi Tian, Yan-Bing Zhang, Jian Song, Cheng-Yun Jin, Sai-Yang Zhang
Summary: FAK, a nonreceptor intracellular tyrosine kinase, is overexpressed in many human cancer cell lines, promoting tumor growth by controlling various cellular functions. Targeting FAK with small molecule inhibitors is considered a promising cancer therapy, with several FAK inhibitors undergoing clinical trials in different phases. Additionally, the development of novel FAK inhibitors, including FAK degraders through PROTAC technology, provides potential for new anticancer agents.
Article
Cell Biology
Rui Wang, Si Wang, Zhen Li, Yuan Luo, Yue Zhao, Qiang Han, Xue-Zhu Rong, Yao-Xing Guo, Yang Liu
Summary: PLEKHH2 is an important oncogene in non-small cell lung cancer (NSCLC). Its expression is correlated with tumor malignancy and is associated with the activation of the PI3K/AKT signaling pathway. PLEKHH2 binds to beta-arrestin1, leading to enhanced FAK phosphorylation and subsequent promotion of lung cancer cell proliferation, migration, and invasion.
CELL DEATH & DISEASE
(2022)
Article
Hematology
Bal Krishan Sharma, Duaa Mureb, Sumit Murab, Leah Rosenfeldt, Brenton Francisco, Rachel Cantrell, Rebekah Karns, Lindsey Romick-Rosendale, Miki Watanabe-Chailland, Jacob Mast, Matthew J. Flick, Patrick W. Whitlock, Joseph S. Palumbo
Summary: The absence of fibrinogen in the tumor microenvironment leads to decreased proliferation and increased senescence in CRC tumors, along with differential expression of genes. Studies suggest that fibrinogen may promote colon cancer growth by regulating cellular proliferation and senescence pathways.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Cell Biology
Ioanna Antoniades, Maria Kyriakou, Anna Charalambous, Katerina Kalalidou, Andri Christodoulou, Maria Christoforou, Paris A. Skourides
Summary: The study successfully prevented the action of FAK at focal adhesions by generating a specific peptide structure, thereby effectively inhibiting the migration and invasion of tumor cells and providing a new direction for the development of anti-metastatic agents.
CELL COMMUNICATION AND SIGNALING
(2021)
Review
Cell Biology
Johanne Le Coq, Ivan Acebron, Barbara Rodrigo Martin, Pilar Lopez Navajas, Daniel Lietha
Summary: In this review, the authors discuss the role of focal adhesion kinase (FAK) in cell-matrix adhesion and migration. They highlight the known structural features of FAK and the challenges in understanding its integration in the focal adhesion complex and the structural changes during focal adhesion maturation.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Xiu-Juan Liu, Xu Liu, Xiao-Jing Pang, Xin-Ying Yuan, Guang-Xi Yu, Yin-Ru Li, Yong-Feng Guan, Yan-Bing Zhang, Jian Song, Qiu-Rong Zhang, Sai-Yang Zhang
Summary: Bruton tyrosine kinase (BTK) plays a key role in B cell antigen receptor signaling pathway and is an important target for treating hematological malignancies and autoimmune diseases. While first-generation BTK inhibitor, Ibrutinib, has contributed significantly to the treatment of B cell malignant tumors, issues such as resistance and miss-target mutations remain. Therefore, there is an urgent need to develop novel BTK inhibitors to address these challenges.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Clinical Neurology
Hae Nim Lee, Seung Jae Hyeon, Heejung Kim, Kyoung Mi Sim, Yunha Kim, Jeongmin Ju, Junghee Lee, Yingxiao Wang, Hoon Ryu, Jihye Seong
Summary: In Huntington's disease, reduced FAK and FA dynamics impair the formation of neurites, leading to synaptic dysfunctions. Mutant HTT associates with phosphatidylinositol 4,5-biphosphate, altering its distribution at the plasma membrane and inhibiting FAK activation.
ACTA NEUROPATHOLOGICA
(2022)
Article
Biochemistry & Molecular Biology
Amita Arora, Annukka M. Kivela, Ling Wang, Rimante Minkeviciene, Juuso H. Taskinen, Birong Zhang, Annika Koponen, Jing Sun, Michiko Shirane, You Zhou, Pirta Hotulainen, Camilla Raiborg, Vesa M. Olkkonen
Summary: During angiogenesis, Protrudin plays a key role in regulating angiogenic tube formation and promoting endothelial cell migration through its effects on FAK activation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Cell Biology
Jingduo Li, Xiupeng Zhang, Zaiyu Hou, Siqi Cai, Yingxue Guo, Limei Sun, Ailin Li, Qingchang Li, Enhua Wang, Yuan Miao
Summary: This study reveals the important role of P130cas in FAK-YAP axis-mediated radioresistance in non-small cell lung cancer (NSCLC). P130cas promotes cell proliferation, alters the cell cycle profile, and enhances tumor growth. Furthermore, the study demonstrates that P130cas interacts with YAP and promotes its activation and nuclear translocation.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Eriko Koide, Mikaela L. Mohardt, Zainab M. Doctor, Annan Yang, Mingfeng Hao, Katherine A. Donovan, Christina C. Kuismi, Alissa J. Nelson, Kathryn Abell, Mike Aguiar, Jianwei Che, Matthew P. Stokes, Tinghu Zhang, Andrew J. Aguirre, Eric S. Fischer, Nathanael S. Gray, Baishan Jiang, Behnam Nabet
Summary: Focal adhesion kinase (FAK) is overexpressed in cancer and is considered as a potential drug target. In this study, a selective FAK inhibitor (BSJ-04-175) and degrader (BSJ-04-146) were developed to evaluate the consequences of abolishing FAK activity in cancer models. Targeted degradation of FAK showed improved activity on downstream signaling and cancer cell viability and migration compared to kinase inhibition.
Article
Gastroenterology & Hepatology
Tao Huang, Yuan-Qing-Xiao Li, Ming-Yu Zhou, Rui-Han Hu, Gao-Liang Zou, Jian-Chao Li, Shu Feng, Yong-Mei Liu, Chang-Qin Xin, Xue-Ke Zhao
Summary: FRNK inhibits aerobic glycolysis in HSCs by inhibiting the FAK/Ras/c-myc/ENO1 pathway, thereby improving liver fibrosis.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)