Primary Lung Cancer Organoids for Personalized Medicine-Are They Ready for Clinical Use?

Abstract

Despite many developments in recent years, non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. Therefore, additional research, aiming to further elucidate the underlying molecular mechanisms of malignant transformation and development of therapy resistance, as well as the identification of additional novel therapeutic avenues, is crucial. For this purpose, reliable in vitro models are indispensable, as they allow for quick identification of suspected oncogenic drivers or evaluation of novel therapeutic strategies in a timely and cost-effective fashion. However, standard two-dimensional cell culture systems, the most frequently used in vitro model, are usually not truly representative of the situation in a patient as these models lack the tumor heterogeneity, the surrounding tumor microenvironment and the three-dimensional complexity of a tumor in vitro. For this reason, 3D cell culture systems, in particular organoids generated from normal non-malignant cells or tumor cell-based organoids (tumoroids), have in recent years gained much attention as alternative in vitro model systems that more closely resemble the actual primary tumor. In this review, we provide an overview of the available literature in the field of NSCLC organoids, which might still be in its infancy, but is gaining momentum.

Keywords: cancer model; non-small cell lung cancer; organoids; personalized medicine; tumoroids.

Figure 1

(A) Primary NSCLC organoids established from fresh cancer tissue. Left: lung adenocarcinoma organoids, right: lung carcinoid organoids. Scale bar: 100 μm. (B) Histomorphological and immunohistochemical characteristics of primary lung squamous cell carcinoma organoids and their respective parental tissue, featuring intracellular keratinization, intercellular bridges and partial p40 positivity. Scale bar: 100 μm (unpublished data, Department of Thoracic Surgery, University Hospital Zurich).