Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

5423 - Development of primary human NSCLC patient derived xenograft and organoids models as a precision approach to tumor treatment

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Oscar Jose Juan Vidal

Citation

Annals of Oncology (2018) 29 (suppl_8): viii649-viii669. 10.1093/annonc/mdy303

Authors

O.J. Juan Vidal1, C. Gandia2, J.M. Pardo-Sánchez2, M. Benet3, S. Aparisi4, S. Palanca5, E. Ansotegui6, C. Jordá7, J.A. Cerón7, N. Mancheño1, M. Sánchez-Céspedes8, A. Lahoz3, J. Carretero4, R. Farràs2

Author affiliations

  • 1 Medical Oncology, Hospital Universitari i Politècnic La Fe, 46026 - Valencia/ES
  • 2 Oncogenic Signalling Lab., Centro de Investigación Príncipe Felipe, 46012 - Valencia/ES
  • 3 Biomarkers And Precision Medicine Unit, Hospital Universitari i Politècnic La Fe, 46026 - Valencia/ES
  • 4 Department Of Physiology, Faculty Of Pharmacy, University of Valencia, 41000 - Valencia/ES
  • 5 Department Of Clinical Analysis, Molecular Biology Unit, Hospital Universitari i Politècnic La Fe, 46026 - Valencia/ES
  • 6 Servicio De Neumología, Hospital Universitari i Politècnic La Fe, 46026 - Valencia/ES
  • 7 Servicio De Cirugía Torácica, Hospital Universitari i Politècnic La Fe, 46026 - Valencia/ES
  • 8 Cancer Epigenetics And Biology Program (pebc), Genes And Cancer Group, Bellvitge Biomedical Research Institute (IDIBELL), 08908 - Hospitalet de Llobregat/ES
More

Resources

Abstract 5423

Background

The prognosis of advanced non-small cell lung cancer (NSCLC) patients is poor. The lack of in vitro models that would faithfully recapitulate the heterogeneity of lung tumors and response to treatment is one of the reasons hampering progress in the development of new therapies. Patient-derived tumor models are becoming the standard for pre-clinical drug testing and biomarker discovery. However, the emerging technology of lung cancer organoids has not yet been broadly implemented in research and have yet to be better established. In this study, our objective was to generate and characterize a collection of NSCLC patient-derived xenograft (PDX) and tumor organoids to demonstrate their applicability to the study of lung cancer.

Methods

Surgically resected tumors were obtained from patients with stage I/II NSCLC during curative-intent surgery. Portions of the tumors were subcutaneous xenografted in NSG mice and expanded 5 passages. In addition, matched portions of tumor and adjacent non-tumor tissues were employed to develop and characterize patient-derived organoids (PDOs). Tumors grew in mice and PDOs were analyzed by histologic and molecular techniques.

Results

We describe the derivation and characterization of 8 PDX models and 20 pairs of PDOs from NSCLC tumors and adjacent non-tumor tissue. PDX could established with a succesful rate of 22,8% (8 out of 35 samples). PDX retain histologic and molecular characteristics of their donors and recapitulate the heterogeneity of human lung tumors. PDOs could be established with a success rate of 100%. We reached a successful long-term expansion of primary NSCLC cells in vitro (> 120 days). Tumor organoids displayed tumor-like cellular morphology and tissue architecture. Tumor-dependent lymphocyte infiltration were observed in these models. We assesed CD45, EpCAM, CD133, CD44 protein expression, as well as Nanog and Oct4 stem cell markers.

Conclusions

We have generated a collection of PDX and PDOs models from NSCLC tumors. These models promise to facilitate the study of cancer stem cell biology and tumor heterogeneity, and may be valuable for drug screening. These models enables the potential long term studies such as the establishment of drug resistant models.

Clinical trial identification

Legal entity responsible for the study

Principe Felipe Research Center.

Funding

Instituto de Salud Carlos III (PI15/00209), co-funded by ERDF.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.