Advances in Src homology 2 domain-containing protein tyrosine phosphatase inhibitors in tumor targeting and immunotherapy
SHI Ge-ge
WANG Zhao-wei
QIU Yue-yuan
HE Lei
LI Zhao-zhao
SHI Jia-xin
ZHAO Bo-chen
HAN Xiao
DU Hai-chen
ZHANG Ying-qi
Abstract：Src homology 2 domain containing protein tyrosine phosphatase 2(SHP2),encoded by the PTPN11 gene,is a member of the PTP family of protein phosphatases.It plays a crucial role in regulating the physiological functions of tumor cells through the RAS-MAPK,PI3K-AKT,and JAK-STAT signaling pathways.Additionally,SHP2 binds to immunosuppressive receptors(such as PD-1 and CTLA4)in the tumor microenvironment,affecting immune cells'function and inhibiting the immune response.Due to its dual functions in regulating both tumor cells and the immune microenvironment,SHP2 is considered a valuable target for tumor therapy.In recent years,numerous SHP2 inhibitors with potential pharmaceutical applications have entered clinical trials,offering new prospects for targeted tumor therapy.However,challenges such as drug resistance,non-specificity,and toxicity still exist in the treatment of tumors using SHP2 inhibitors.Therefore,further researches on the druggability and targeting strategies of SHP2 inhibitors are necessary.This article provides a comprehensive summary of the regulatory mechanism of SHP2 in signaling pathways,the role in tumors and the immune microenvironment,and reviews the progress of clinical research on SHP2 inhibitors.
Keywords：Src homology 2 domain-containing protein tyrosine phosphatase 2tumorsignal pathwaytumor immune microenvironmentSrc homology 2 domain-containing protein tyrosine phosphatase inhibitor
Publication Date：2024-08-15
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：7( 1557-1563 )