Genome-wide CRISPR/Cas9 Screens Reveal Shared and Bespoke Mechanisms of Resistance to SHP2 inhibition

W Wei - 2023 - search.proquest.com
Abstract SHP2 (PTPN11) acts upstream of SOS1/2 to enable RAS activation. Allosteric
SHP2 inhibitors (SHP2i) in the clinic prevent SHP2 activation, block proliferation of RTK-or …

Genome-wide CRISPR/Cas9 screens reveal shared and cell-specific mechanisms of resistance to SHP2 inhibition

W Wei, MJ Geer, X Guo, I Dolgalev… - Journal of Experimental …, 2023 - rupress.org
SHP2 (PTPN11) acts upstream of SOS1/2 to enable RAS activation. Allosteric SHP2
inhibitors (SHP2i) in the clinic prevent SHP2 activation, block proliferation of RTK-or cycling …

Mechanisms of resistance to SHP2 inhibition

W Wei, M Geer, X Guo, N Sanjana, BG Neel - Cancer Research, 2022 - AACR
Abstract SHP2 (PTPN11) is required for RAS activation, acting upstream of SOS1/2.
Allosteric SHP2 inhibitors (SHP2is) stabilize auto-inhibition mediated by N-SH2/PTP …

[HTML][HTML] Sidestepping SHP2 inhibition

B Popescu, K Shannon - The Journal of Experimental Medicine, 2023 - ncbi.nlm.nih.gov
Allosteric SHP2 inhibitors are a novel class of compounds that target hyperactive
Ras/Mitogen Activated Protein Kinase (MAPK) signaling. In this issue of JEM, Wei et …

SHP2 Inhibition Abrogates MEK inhibitor Resistance in Multiple Cancer Models

C Fedele, H Ran, B Diskin, W Wei, J Jen, K Araki… - bioRxiv, 2018 - biorxiv.org
Adaptive resistance to MEK inhibitors (MEK-Is) typically occurs via induction of genes for
different receptor tyrosine kinases (RTKs) and/or their ligands, even in tumors of the same …

Genome-Wide CRISPR Screens Identify Multiple Synthetic Lethal Targets That Enhance KRASG12C Inhibitor Efficacy

S Mukhopadhyay, HY Huang, Z Lin, M Ranieri, S Li… - Cancer Research, 2023 - AACR
Non–small lung cancers (NSCLC) frequently (∼ 30%) harbor KRAS driver mutations, half of
which are KRAS G12C. KRAS-mutant NSCLC with comutated STK11 and/or KEAP1 is …

CRISPR Screening Identifies Mechanisms of Resistance to KRASG12C and SHP2 Inhibitor Combinations in Non–Small Cell Lung Cancer

A Prahallad, A Weiss, H Voshol, G Kerr, K Sprouffske… - Cancer Research, 2023 - AACR
Although KRASG12C inhibitors show clinical activity in patients with KRAS G12C mutated
non–small cell lung cancer (NSCLC) and other solid tumor malignancies, response is …

SHP2 Inhibition Abrogates Adaptive Resistance to KRASG12C-Inhibition and Remodels the Tumor Microenvironment of KRAS-Mutant Tumors

C Fedele, S Li, KW Teng, C Foster, D Peng, H Ran… - bioRxiv, 2020 - biorxiv.org
ABSTRACT KRAS is the most frequently mutated oncogene in human cancer, and KRAS
inhibition has been a longtime therapeutic goal. Recently, inhibitors (G12C-Is) that bind …

RAS nucleotide cycling underlies the SHP2 phosphatase dependence of mutant BRAF-, NF1-and RAS-driven cancers

RJ Nichols, F Haderk, C Stahlhut, CJ Schulze… - Nature cell …, 2018 - nature.com
Oncogenic alterations in the RAS/RAF/MEK/ERK pathway drive the growth of a wide
spectrum of cancers. While BRAF and MEK inhibitors are efficacious against BRAFV600E …

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
Adaptive resistance to MEK inhibitors (MEKi) typically occurs via induction of genes for
different receptor tyrosine kinases (RTK) and/or their ligands, even in tumors of the same …