Tumor intrinsic efficacy by SHP2 and RTK inhibitors in KRAS-mutant cancers

HX Hao, H Wang, C Liu, S Kovats, R Velazquez… - Molecular cancer …, 2019 - AACR
… that the effect of SHP2 inhibition in KRAS-mutant cancers could be recapitulated with RTK
inhibitors. We first evaluated the efficacy of an RTK inhibitor cocktail, targeting ERBBs, FGFRs, …

KRAS mutation: from undruggable to druggable in cancer

L Huang, Z Guo, F Wang, L Fu - Signal transduction and targeted …, 2021 - nature.com
… were associated with genomic aberrations that were associated with the RAS/RTK pathway
79 . … Selective inhibitors targeting specific KRAS mutations are urgently needed to effectively …

SHP2 inhibition overcomes RTK-mediated pathway reactivation in KRAS-mutant tumors treated with MEK inhibitors

H Lu, C Liu, R Velazquez, H Wang, LM Dunkl… - Molecular cancer …, 2019 - AACR
… MEK inhibition, using an SHP2 inhibitor (SHP099) that blocks RAS activation mediated
by multiple RTKs. We find that RTK-driven feedback activation widely exists in KRAS-mutant

[HTML][HTML] Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers

H Ebi, RB Corcoran, A Singh, Z Chen… - The Journal of …, 2011 - Am Soc Clin Investig
… robust apoptosis of human KRAS mutant colorectal cancer cell … for utilizing RTK inhibitors
in the treatment of KRAS mutantRTK (most often IGF-IR) and MEK inhibitor for KRAS mutant

The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients

J Hallin, LD Engstrom, L Hargis, A Calinisan, R Aranda… - Cancer discovery, 2020 - AACR
… upstream signaling with RTK inhibitors that increase the activity of KRAS G12C … RTK
signaling to KRAS. Accordingly, SHP2 inhibitors are active in cancers driven by KRAS mutations

Targeting KRAS mutant lung cancer: light at the end of the tunnel

M Drosten, M Barbacid - Molecular oncology, 2022 - Wiley Online Library
… effect of RTK inhibition may be … inhibition could be effective in patients with KRAS mutant
lung tumors [[114]]. Interestingly, CDK4/6 inhibitors also synergized with KRAS G12C inhibitors

Escaping KRAS: gaining autonomy and resistance to KRAS inhibition in KRAS mutant cancers

Y Adachi, R Kimura, K Hirade, H Ebi - Cancers, 2021 - mdpi.com
… lung cancer, EMT has been shown to play a defining role in the feedback reactivation of
RTK signaling following MEK inhibition. In epithelial-like cells, this feedback was mediated by …

Genetic events that limit the efficacy of MEK and RTK inhibitor therapies in a mouse model of KRAS-driven pancreatic cancer

P Pettazzoni, A Viale, P Shah, A Carugo, H Ying… - Cancer research, 2015 - AACR
RTK activated upon MEK inhibition, we performed RPPA analysis on iKRAS cells exposed to
single RTK inhibitors … To inhibit each RTK, we used the dual EGFR–HER2 inhibitor lapatinib…

Breaking oncogene addiction: getting RTK/RAS-mutated cancers off the SOS

E Sheffels, RL Kortum - Journal of Medicinal Chemistry, 2021 - ACS Publications
… survival in KRAS mutant cancer cells, (… inhibitor of proximal RTK signaling may be a common
therapeutic strategy to enhance RTK inhibitor efficacy and treat cancers dependent on RTK

Key roles of EMT for adaptive resistance to MEK inhibitor in KRAS mutant lung cancer

H Kitai, H Ebi - Small GTPases, 2017 - Taylor & Francis
… of KRAS and RTK inhibitorsinhibition leads to distinct activation of RTKs in KRAS mutant
lung cancers depending on the epithelial or mesenchymal state of the cancer. While inhibitors