Patient-derived spheroids and patient-derived organoids simulate evolutions of lung cancer

Lung cancer has become the primary cause of cancer-related deaths because of its high recurrence rate, ability to metastasise easily, and propensity to develop drug resistance. The wide-ranging heterogeneity of lung cancer subtypes increases the complexity of developing effective therapeutic interventions. Therefore, personalised diagnostic and treatment strategies are required to guide clinical practice. The advent of innovative three-dimensional (3D) culture systems such as organoid and organ-on-a-chip models provides opportunities to address these challenges and revolutionise lung cancer research and drug evaluation. In this review, we introduce the advancements in lung-related 3D culture systems, with a particular focus on lung organoids and lung-on-a-chip, and their latest contributions to lung cancer research and drug evaluation. These developments include various aspects, from authentic simulations and mechanistic enquiries into lung cancer to assessing chemotherapeutic agents and targeted therapeutic interventions. The new 3D culture system can mimic the pathological and physiological microenvironment of the lung, enabling it to supplement or replace existing two-dimensional culture models and animal experimental models and realize the potential for personalised lung cancer treatment.

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Alveolar Organoids in Lung Disease Modeling

Purev,

Bahmed,

Kosmider

2024

Biomolecules

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Lung organoids display a tissue-specific functional phenomenon and mimic the features of the original organ. They can reflect the properties of the cells, such as morphology, polarity, proliferation rate, gene expression, and genomic profile. Alveolar type 2 (AT2) cells have a stem cell potential in the adult lung. They produce and secrete pulmonary surfactant and proliferate to restore the epithelium after damage. Therefore, AT2 cells are used to generate alveolar organoids and can recapitulate distal lung structures. Also, AT2 cells in human-induced pluripotent stem cell (iPSC)-)-derived alveolospheres express surfactant proteins and other factors, indicating their application as suitable models for studying cell–cell interactions. Recently, they have been utilized to define mechanisms of disease development, such as COVID-19, lung cancer, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. In this review, we show lung organoid applications in various pulmonary diseases, drug screening, and personalized medicine. In addition, stem cell-based therapeutics and approaches relevant to lung repair were highlighted. We also described the signaling pathways and epigenetic regulation of lung regeneration. It is critical to identify novel regulators of alveolar organoid generations to promote lung repair in pulmonary diseases.

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Patient-derived spheroids and patient-derived organoids simulate evolutions of lung cancer

Cited by 3 publications

References 67 publications

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Alveolar Organoids in Lung Disease Modeling

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