EGFR Blockade Reverts Resistance to KRASG12C Inhibition in Colorectal Cancer

Amodio, Vito; Yaeger, Rona; Arcella, Pamela; Cancelliere, Carlotta; Lamba, Simona; Lorenzato, Annalisa; Arena, Sabrina; Montone, Monica; Mussolin, Benedetta; Bian, Yu; Whaley, Adele; Pinnelli, Marika; Murciano‐Goroff, Yonina R.; Vakiani, Efsevia; Valeri, Nicola; Liao, Wei‐Li; Bhalkikar, Anuja; Thyparambil, Sheeno; Zhao, HuiYong; Stanchina, Elisa de; Marsoni, Silvia; Siena, Salvatore; Bertotti, Andrea; Trusolino, Livio; Li, Bob T.; Rosen, Neal; Nicolantonio, Federica Di; Bardelli, Alberto; Misale, Sandra

doi:10.1158/2159-8290.cd-20-0187

articleCancer DiscoveryMay 19, 2020BRONZE OA

EGFR Blockade Reverts Resistance to KRASG12C Inhibition in Colorectal Cancer

VAVito Amodio RYRona Yaeger PAPamela Arcella CCCarlotta Cancelliere SLSimona Lamba

Candiolo Cancer Institute · Memorial Sloan Kettering Cancer Center · +7 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Abstract Most patients with KRASG12C–mutant non–small cell lung cancer (NSCLC) experience clinical benefit from selective KRASG12C inhibition, whereas patients with colorectal cancer bearing the same mutation rarely respond. To investigate the cause of the limited efficacy of KRASG12C inhibitors in colorectal cancer, we examined the effects of AMG510 in KRASG12C colorectal cancer cell lines. Unlike NSCLC cell lines, KRASG12C colorectal cancer models have high basal receptor tyrosine kinase (RTK) activation and are responsive to growth factor stimulation. In colorectal cancer lines, KRASG12C inhibition induces higher phospho-ERK rebound than in NSCLC cells. Although upstream activation of several RTKs…

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483

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FWCI: 20.88
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Topics & keywords

Topics

Keywords

Blockade
Colorectal cancer
Cancer research
Cancer
Medicine
Internal medicine
Receptor

UN Sustainable Development Goals

Good health and well-being

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