Meng Liu, Shan Gao, Reham M. Elhassan, Xuben Hou, Hao Fang. Strategies to overcome drug resistance using SHP2 inhibitors[J]. Acta Pharmaceutica Sinica B, 2021, 11(12): 3908-3924

Strategies to overcome drug resistance using SHP2 inhibitors
Meng Liu, Shan Gao, Reham M. Elhassan, Xuben Hou, Hao Fang
School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Encoded by PTPN11, the SHP2 (Src homology-2 domain-containing protein tyrosine phosphatase-2) is widely recognized as a carcinogenic phosphatase. As a promising anti-cancer drug target, SHP2 regulates many signaling pathways such as RAS-RAF-ERK, PI3K-AKT and JAK-STAT. Meanwhile, SHP2 plays a significant role in regulating immune cell function in the tumor microenvironment. Heretofore, five SHP2 allosteric inhibitors have been recruited in clinical studies for the treatment of cancer. Most recently, studies have proved the therapeutic potential of SHP2 inhibitor in overcoming drug resistance of kinase inhibitors and programmed cell death-1 (PD-1) blockade. Herein, we review the structure, function and small molecular inhibitors of SHP2, and highlight recent progress in overcoming drug resistance using SHP2 inhibitor. We hope this review would facilitate the future clinical development of SHP2 inhibitors.
Key words:    SHP2 inhibitor    Allosteric inhibitor    Anti-cancer    Drug resistance   
Received: 2021-01-02     Revised: 2021-03-08
DOI: 10.1016/j.apsb.2021.03.037
Funds: This work was supported by National Natural Science Foundation of China (Grant No. 81874288, 92053105 and 82003590), Natural Science Foundation of Shandong Province (ZR2020QH342, China) and the Young Scholars Program of Shandong University (China).
Corresponding author: Xuben Hou,;Hao Fang,;
Author description:
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Meng Liu
Shan Gao
Reham M. Elhassan
Xuben Hou
Hao Fang

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