SHP2 inhibition prevents adaptive resistance to MEK inhibitors in multiple cancer models

C Fedele, H Ran, B Diskin, W Wei, J Jen, MJ Geer… - Cancer discovery, 2018 - AACR
… To explore whether SHP2 inhibition could suppress MEKi adaptive resistance, we
performed in vitro viability (PrestoBlue) and colony formation assays on a panel of KRAS-mutant …

[HTML][HTML] 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

Shipping out MEK inhibitor resistance with SHP2 inhibitors

P Torres-Ayuso, J Brognard - Cancer discovery, 2018 - AACR
… Fedele and colleagues demonstrate that SHP2 inhibitors prevent adaptive MEK inhibitor
resistance; therefore, combining MEK and SHP2 inhibitors represents an exciting new …

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 …

[HTML][HTML] 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 …