Lung Cancer Organoids: The Rough Path to Personalized Medicine

SIMPLE SUMMARY: Lung cancer is very difficult to cure, especially when it has spread to other parts of the body. One of the main reasons that delay the identification of effective therapies is the complexity of lung cancer cells, which can be very different among individual patients. Organoids are small aggregates of tumor cells that are generated from lung tumors and used in cancer research laboratories to study the features of tumor cells. Organoids have unique properties, as they reproduce many characteristics of the tumor derived from each specific patient. Due to their capacity to reproduce individual tumor features in the laboratory setting, organoids are an excellent system to study lung cancer and to identify functional therapies. This review summarizes the challenges encountered by researchers in the field of lung cancer organoids and describes how the advances in organoid technology may allow the future development of individualized therapies for lung cancer patients. ABSTRACT: Lung cancer is the leading cause of cancer death worldwide. Despite significant advances in research and therapy, a dismal 5-year survival rate of only 10–20% urges the development of reliable preclinical models and effective therapeutic tools. Lung cancer is characterized by a high degree of heterogeneity in its histology, a genomic landscape, and response to therapies that has been traditionally difficult to reproduce in preclinical models. However, the advent of three-dimensional culture technologies has opened new perspectives to recapitulate in vitro individualized tumor features and to anticipate treatment efficacy. The generation of lung cancer organoids (LCOs) has encountered greater challenges as compared to organoids derived from other tumors. In the last two years, many efforts have been dedicated to optimizing LCO-based platforms, resulting in improved rates of LCO production, purity, culture timing, and long-term expansion. However, due to the complexity of lung cancer, further advances are required in order to meet clinical needs. Here, we discuss the evolution of LCO technology and the use of LCOs in basic and translational lung cancer research. Although the field of LCOs is still in its infancy, its prospective development will likely lead to new strategies for drug testing and biomarker identification, thus allowing a more personalized therapeutic approach for lung cancer patients.