Abstract LB-B05: Characterization of a panel of 79 PDX-derived cell lines with a focus on the EGFR exon 20 insertion mutation-driven NSCLC model LXFE 2478

Abstract

Abstract Patient-derived tumor xenograft (PDX) models have become indispensable for the preclinical profiling of novel anti-cancer agents as they retain histological, molecular and pharmacological characteristics of the parental patient tumors and for many tumor types collectively replicate the diversity of patient tumors. To make PDX models available for in vitro assays, we have established a panel of 79 low passage cell lines derived from PDXs representing 15 different tumor histologies. Using, among others, the non-small cell lung cancer model LXFE_2478 which is driven by the exon 20 insertion EGFR mutation M766_A767insASV as an example, we demonstrate the following similarities of PDX models and the corresponding PDX-derived cell lines. (i) Subcutaneous xenografts established from PDX-derived cell lines mirror the histology of the corresponding PDX models and usually also patient tumors. (ii) For LXFE_2478 both the PDX model and the corresponding PDX-derived cell line express high levels of EGFR, suggesting that the oncogenic driver is still present. (iii) For LXFE_2478 the PDX and the PDX-derived cell line subcutaneously implanted in mice display comparable sensitivity to a variety of EGFR inhibitors and cytotoxics. (iv) For LXFE_2478 the sensitivity of the PDX-derived cell line to a variety of EGFR inhibitors in an in vitro 2D cell survival and proliferation assay in general corresponds to the EGFRi sensitivity of the corresponding PDX model in vivo. (v) For several additional PDX models representing various histotypes the sensitivity to first generation EGFR inhibitors of PDX-derived cell lines in the 2D assay is in line with the in vivo EGFR inhibitor sensitivity of the corresponding PDXs. In conclusion, at least for some mechanisms of action in vitro data obtained with PDX-derived cell lines can predict the in vivo behavior of the corresponding PDX model and can thereby accelerate, and reduce the costs of, the discovery of novel anticancer agents. Citation Format: Gerhard Kelter, Anne-Lise Peille, Jutta Fehr, Hagen Klett, Armin Maier, Markus Posch, Thomas M Metz. Characterization of a panel of 79 PDX-derived cell lines with a focus on the EGFR exon 20 insertion mutation-driven NSCLC model LXFE 2478 [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr LB-B05. doi:10.1158/1535-7163.TARG-19-LB-B05