Abstract 4801: Collection of lung cancer patient-derived xenograft (PDX) models to evaluate precision therapeutic strategies

Abstract

Abstract Background: Translational cancer research needs appropriated preclinical models to discover predictive biomarkers and evaluate precision therapeutic strategies. Conventional available preclinical models have proven not been optimal to this end, since cell lines based xenografts do not reconstitute the complexity of human cancer and carry acquired mutations not found in the original tumor. For these reasons our aim was generate and completely characterize a collection of non-small cell lung cancer (NSCLC) PDX models useful for translational lung cancer research. Materials and methods: Resected primary tumors from NSCLC patients were subcutaneous xenografted in athymic nude mice and expanded in successive groups of mice to get a perpetual live bank of each tumor. Every tumor, which successfully grew in mice, was analyzed by histologic and molecular techniques (NGS gene panel, exome and RNA Seq). Furthermore, a bank of frozen pieces of tumor was expanded and stored in order to generate later cohorts of tumor-bearing mice suitable for preclinical drug evaluation. Results: Our collection consists on 42 PDX models (26 SCC, 12ADC, 3LCC). We have characterized all of them histologically and molecularly with a 22 genes NGS panel. Furthermore, we have analyzed the exome and transcriptome of 33 models (20 SCC, 10 ADC and 3 LCC). All PDX models mostly retain the principal histologic and molecular characteristics of their donors and recapitulate the heterogeneity of human lung tumors. In our PDX collection we have sufficiently represented all the NSCLC histology and the most relevant molecular alterations in lung cancer in order to perform precision medicine evaluation studies. Conclusions: We have generated a collection of 42 PDX models of NSCLC characterized at the histological, genomic and transcriptomic level, which represents the most frequent histological and molecular subtypes of this type of lung cancer. This collection will be really useful to integrate drug screening with biomarker discovery and to evaluate precision therapeutic strategies. Our future aim will be to use this collection for biomarkers identification and preclinical evaluation of new therapeutic strategies targeted to bad prognostic lung tumors with suboptimal therapeutic approaches. Citation Format: Sonia Molina-Pinelo, Ricardo Melendez, Rocío Suarez, Laura García, Laura Ojeda, Nicolas Moreno, María V Guijarro, Luis Paz-Ares, Irene Ferrer. Collection of lung cancer patient-derived xenograft (PDX) models to evaluate precision therapeutic strategies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4801. doi:10.1158/1538-7445.AM2017-4801