1524P - Generation and characterization of a collection of patient-derived xenografts (PDX) models for translational lung cancer research

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Translational Research
Presenter Sonia Molina-Pinelo
Citation Annals of Oncology (2016) 27 (6): 526-544. 10.1093/annonc/mdw392
Authors S. Molina-Pinelo1, R. Meléndez2, R. Suarez1, L. García1, L. Ojeda3, P. Yague3, L. Paz-Ares4, I. Ferrer1
  • 1H12o-cnio Lung Cancer Clinical Research Unit, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 2Instituto De Biomedicina De Sevilla, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
  • 3H12o-cnio Lung Cancer Clinical Research Unit, University Hospital 12 De Octubre, Madrid/ES
  • 4Medical Oncology, Hospital Universitario Doce de Octubre, 28041 - Madrid/ES

Abstract

Background

The use of good preclinical models is essential in translational cancer research. An appropriate preclinical model must be useful for drug screening, biomarker discovery and preclinical evaluation of precision therapeutic strategies. Conventional available preclinical models are not optimal to this end. Xenografts from cell lines do not reconstitute the architecture and environment of human cancer and acquire mutations not found in the original tumor. Our aim is to generate and characterize a collection of PDX models for translational lung cancer research by implantation of lung primary human tumors in mice. Mainly, this collection will be used for biomarker identification and preclinical evaluation of new therapeutic strategies targeted to bad prognostic lung tumors with suboptimal therapeutic approaches.

Methods

Resected NSCLC from patients were subcutaneous xenografted and expanded in successive groups of nude mice to get a perpetual live bank of each tumor. Every tumor, which successfully grew in mice, was used to analyze the exome and transcriptome by NGS techniques. Furthermore, a bank of frozen pieces of tumor was stored in order to generate later cohorts of tumor-bearing mice suitable for preclinical drug evaluation and biomarker identification.

Results

We have characterized 32 different PDX models at the genomic and transcriptomic level: 20 SCC, 10 ADC and 2 LCC. The 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 and characterize a collection of PDX models of NSCLC, which represents the most frequent histological and molecular subtypes of this type of LC. This collection will be really useful to integrate drug screening with biomarker discovery and to evaluate precision therapeutic strategies preclinically. Our future aim will be to use this collection in order to identify new effective therapeutic strategies targeted to bad prognostic subtypes of lung cancer.

Clinical trial identification

Legal entity responsible for the study

IF is funded by Fundacion AECC and Consejería de Salud de la Junta de Andalucía (PI-0029-2013). SMP is funded by Consejería de Salud y Bienestar Social (PI-0046-2012), and Fundación Mutua Madrileña (2014). LPA is funded by Fondo de Investigación Sanitaria (1401964) and RTICC (R12/0036/0028).

Funding

None

Disclosure

All authors have declared no conflicts of interest.