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

SIMPLE SUMMARY: Identification of novel therapeutic strategies for the treatment of non-small cell lung cancer (NSCLC) remains an urgent need in the area of lung cancer research. Traditional in vitro cell culture systems form one of the corner stones of cancer research. However, the growth of cancer cells in a two-dimensional pattern on a plastic dish in artificial conditions is not ideal, as the growth pattern significantly differs from that of a complex tumor in a patient. Hence, in recent years, efforts have been undertaken to generate more complex three-dimensional in vitro models, so-called organoid or tumoroid models, that more closely resemble the growth pattern and tumor heterogeneity observed in a patient. In this review, we summarize the efforts thus far undertaken in the area of NSCLC organoid development. 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.