Ai-20 * Mechanisms of Resistance to Egfr Inhibition Associated With an Invasive Phenotype
Year: 2014
Type: conference-abstract
Abstract: To date, strategies targeting epidermal growth factor receptor (EGFR) signaling in glioblastoma (GBM) have had disappointing results in the clinic. One mechanism of resistance is thought to be the diversity of signaling pathways driving proliferation in GBM; however, given the heterogeneity of GBM, other mechanisms likely drive resistance as well. Using a murine model for GBM, we investigated whether altered tumor cell invasion may be one mechanism driving tumor resistance. To analyze tumor cell invasion, we employed 2D invasion chambers, 3D matrigel invasion assays and in vivo tumor growth. Using a panel of EGFR inhibitors, we demonstrate that in select tumor progenitor cells inhibition of EGFR induces a pro-invasive phenotype. Interestingly, the pro-invasive phenotype is specific to inhibition of EGFR and is not conferred by inhibition of many pathways downstream of EGFR, including Src, Akt, PI3K, and Erk. Moreover, the pro-invasive phenotype is recapitulated in vivo upon inhibition of EGFR. Our data suggest that alterations in tumor cell invasion may be an additional and unexpected consequence of inhibition of EGFR. We will present our current data investigating the molecular basis of this response and how the response might be predicted in human tumors.
Source: Neuro-Oncology
Authors: A. McKinney, J. Engler, J. Phillips
Institution: University of California, San Francisco
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2327983157