Several studies have shown that SHP2 plays an important role in regulating immune cell functions in tumor microenvironment. A few clinical trials conducted using SHP2 allosteric inhibitors have shown remarkable anti-tumor benefits and good safety profiles.

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 …

Nov 21, 2024 · Given their expression and crucial roles in both tumor and immune cells, SHP1 and SHP2 represent promising drug targets for antitumor therapeutic interventions. Recent publications revealed that SHP1 or SHP2 deficiency, either alone or in combination with chemotherapy or immune therapy, exhibits potent antitumor and immune-boosting activities ...

In view of this, we comprehensively and thoroughly reviewed literatures about SHP2 regulatory mechanisms, substrates and binding partners, biological functions, roles in human cancers, and different classes of small molecule inhibitors target this oncoprotein in cancer.

Dec 29, 2022 · SHP-2 and the PD-1-SHP-2 signaling restrained the GM-CSF-mediated phosphorylation of HOXA10 and IRF8, which induce myeloid differentiation and monocyte/DC lineage commitment, respectively.

Jan 4, 2023 · In this chapter, we comprehensively summarize the multifaceted functions of SHP2 and the structural basis of SHP2 under different conditions. Additionally, the challenges and prospects of SHP2-targeted drug discovery are also discussed.

As SHP2 is at the crossroads of many functions and pathways, this molecule can be leveraged for therapeutic targeting in cancer. SHP2 inhibitors have shown promise in overcoming resistance to kinase inhibitors and PD-1 blockade by hindering the …

Oct 22, 2020 · Recent discovery of allosteric inhibitors has inspired a novel approach to selectively target SHP2 via the noncatalytic site. To date, four SHP2 allosteric inhibitors have entered clinical trials for the treatment of solid tumors.

Oct 25, 2019 · SHP-2 possesses two N-terminal SH2 domains (N-SH2 and C-SH2) and a central protein tyrosine phosphatase (PTP) core (Figure 1) (3, 4, 27 – 30). The PTP domain is highly conserved among classical PTP phosphatases and is …

Nov 1, 2023 · SHP2 modulates the signaling downstream of oncogenic RTKs and is found hyperactivated in gastric carcinoma (4), anaplastic large cell lymphoma (5), glioblastoma (6), and breast cancer (7), and mediates the oncogenic signals of EGFR- and KRAS-driven cancers (8, 9).