SHP2 drives adaptive resistance to ERK signaling inhibition in molecularly defined subsets of ERK-dependent tumors

TA Ahmed, C Adamopoulos, Z Karoulia, X Wu… - Cell reports, 2019 - cell.com
… ERK signaling and the SHP2 phosphatase prevents adaptive resistance in defined subsets
… , p(Y542)SHP2 induction was observed in response to ERK signaling inhibition. The strategy …

[HTML][HTML] Strategies to overcome drug resistance using SHP2 inhibitors

M Liu, S Gao, RM Elhassan, X Hou, H Fang - Acta Pharmaceutica Sinica B, 2021 - Elsevier
… and functions of SHP2, and briefly review the development of SHP2 inhibitors. Importantly, …
to overcome drug resistance and synergistic tumor immunotherapy using SHP2 inhibitors. We …

SHP2 inhibition mitigates adaptive resistance to MEK inhibitors in KRAS-mutant gastric cancer through the suppression of KSR1 activity

W Zheng, Z Yang, P Song, Y Sun, P Liu, L Yue, K Lv… - Cancer Letters, 2023 - Elsevier
… , SHP2SHP2, during adaptive resistance to MEKis, impaired the interaction with KSR1,
activating KSR1 to promote MAPK signaling. In conclusion, SHP2 promotes adaptive resistance

Overriding adaptive resistance to sorafenib via combination therapy with SHP2 blockade in hepatocellular carcinoma

CON Leung, M Tong, KPS Chung, L Zhou, N Che… - Hepatology, 2020 - hub.hku.hk
SHP2 blockade by SHP099 in combination with sorafenib attenuated the adaptive resistance
… Our results suggest that SHP2 inhibition could be a potential strategy to override sorafenib …

Strategies targeting protein tyrosine phosphatase SHP2 for cancer therapy

Y Song, S Wang, M Zhao, X Yang… - Journal of medicinal …, 2022 - ACS Publications
… To date, eight SHP2 inhibitors have advanced into clinical trials as … adaptive resistant
cancers. In this Perspective, we briefly summarize the strategies targeting SHP2 including inhibitors

SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling

C Fedele, S Li, KW Teng, CJR Foster, D Peng… - Journal of Experimental …, 2020 - rupress.org
… Here, by using two new affinity reagents that allow direct monitoring of KRAS G12C
activation and inhibition, we find that G12C-Is evoke adaptive resistance in vitro and in vivo by …

Overcoming Immune Checkpoint Therapy Resistance with SHP2 Inhibition in Cancer and Immune Cells: A Review of the Literature and Novel Combinatorial …

A Tojjari, A Saeed, A Sadeghipour, R Kurzrock… - Cancers, 2023 - mdpi.com
… have shown promise in overcoming resistance to kinase inhibitorsSHP2 inhibitors are
used to overcome drug resistance, especially to immunotherapy agents. Many SHP2 inhibitors

Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRASG12C Inhibition

MB Ryan, F Fece de la Cruz, S Phat, DT Myers… - Clinical cancer …, 2020 - AACR
inhibitors, SHP2 inhibitors, and MEK/ERK inhibitors were assessed in combination with KRAS
G12C inhibitors … suggest that SHP2 inhibition can abrogate adaptive feedback reactivation …

Overriding adaptive resistance to sorafenib through combination therapy with src homology 2 domain–containing phosphatase 2 blockade in hepatocellular …

CON Leung, M Tong, KPS Chung, L Zhou, N Che… - …, 2020 - Wiley Online Library
… -resistant cell lines as well as patient-derived xenografts. Upon sorafenib treatment, adaptive
resistance … We found that the SHP2 inhibitor SHP099 abrogated sorafenib resistance in …

Phosphorylation of SHP2 at Tyr62 Enables Acquired Resistance to SHP2 Allosteric Inhibitors in FLT3-ITD–Driven AML

A Pfeiffer, G Franciosa, M Locard-Paulet, I Piga… - Cancer research, 2022 - AACR
… We further investigated the role of SHP2 phosphorylation on Tyr62 … of adaptive resistance
through reactivation of the SHP2-RAS-ERK axis. Finally, we show that this adaptive resistance