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.
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.
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.
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.
Instituto de Salud Carlos III (PI15/00209), co-funded by ERDF.
All authors have declared no conflicts of interest.