Abstract 2813: Tumor Models Driven by EGFR: Optimizing the Preclinical Profiling of EGFR-targeting Agents

Abstract The epidermal growth factor receptor (EGFR, HER1, ERBB1) is a driver of many human cancers. Standard of care treatment for colon, head and neck and non-small cell lung cancer includes drugs targeting EGFR. Numerous molecular alterations activating the oncogenic potential of the EGFR gene have been described including activating point mutations, point mutations causing resistance against EGFR-targeting drugs, activating deletions and truncations as well as overexpression of EGFR and its ligands, occasionally induced by gene amplification. In other situations, EGFR has been identified as a driver in the absence of any obvious molecular alterations of the EGFR gene. The discovery and development of EGFR-targeting agents depends on the availability of relevant tumor models. We provide an overview of our collection of EGFR-driven tumor models, including PDXs along with PDX-derived cell lines and human tumor cell lines. We compare sensitivity profiles of tumor models for EGFR-targeting agents obtained in vivo and in vitro and demonstrate that for EGFR-targeting agents, data obtained in 2D and 3D assays are predictive for the in vivo situation. We propose an optimized strategy for the preclinical profiling of EGFR-targeting anti-cancer agents. Citation Format: Markus Posch, Hagen Klett, Anne-Lise Peille, Gerhard Kelter, Armin Maier, Julia Schüler, Thomas M. Metz. Tumor models driven by EGFR: Optimizing the preclinical profiling of EGFR-targeting agents [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2813.