Patient-Derived Organoids as a Stem Cell Model to Study Lung Cancer

Lung cancer is an extremely aggressive disease that remains the most common cause of cancer-related death in the world. However, to date the lack of functional models that truly represent the heterogeneity and three-dimensional complexity of the tumor has impeded the implementation of personalized medicine. In recent years, lung cancer organoids (LCOs) have emerged as a stem cell based in vitro model that closely resembles the original tumor. In this chapter, we provide a comprehensive review on LCOs including the characterization of the stem cells of origin, the description of culture media and principal culture protocols used, and the main applications for this model. LCOs can be obtained from a pool of stem cells present in the tumor of origin (known as cancer stem cells), thus generating different types of LCOs. LCOs have the ability to retain the histological and genetic features of their corresponding samples. To achieve satisfactory organoid establishment and long-term growth, complex culture methodology and media are necessary. However, there is still a need to optimize the LCO culture protocols since problems such as the normal lung organoid contamination can affect the results of drug screening studies. Moreover, LCOs have a great potential also for basic research on cancer stem cells or on tumor microenvironment studies among others. Patient-derived LCOs are highly promising stem cell models that reproduce the in vivo architecture and function of the native lung tissue, can be maintained in long-term cultures, and have a huge potential for preclinical studies in the field of personalized cancer medicine.