Lung cancer organoid-based drug evaluation models and new drug development application trends

Abstract

Lung cancer is a malignant tumor with high incidence and mortality rates in both men and women worldwide. Although anticancer drugs are prescribed to treat lung cancer patients, individual responses to these drugs vary, making it crucial to identify the most suitable treatment for each patient. Therefore, it is necessary to develop an anticancer drug efficacy prediction model that can analyze drug efficacy before patient treatment and establish personalized treatment strategies. Unlike two-dimensional (2D) cultured lung cancer cells, lung cancer organoid (LCO) models have a three-dimensional (3D) structure that effectively mimics the characteristics and heterogeneity of lung cancer cells. Lung cancer patient-derived organoids (PDOs) also have the advantage of recapitulating histological and genetic characteristics similar to those of patient tissues under in vitro conditions. Due to these advantages, LCO models are utilized in various fields, including cancer research, and precision medicine, and are especially employed in various new drug development processes, such as targeted therapies and immunotherapy. LCO models demonstrate potential applications in precision medicine and new drug development research. This review discusses the various methods for implementing LCO models, LCO-based anticancer drug efficacy analysis models, and new trends in lung cancer-targeted drug development.

Keywords: Lung cancer organoid models (LCO models); drug discovery; high-throughput screening (HTS); new drug development; precision medicine.

Figure 1

Cell source processing schematic for producing lung cancer PDO model. Lung cancer organoids are formed by isolating single cells through the patient’s tumor or malignant pleural effusions and mixing them with ECM. Organoids are cultured using a medium containing EGF, FGF7, Noggin, etc. Lung cancer organoid models can be formed using methods such as 3D-embedded culture, hanging drop culture, ALI culture, 3D bioreactor, and lung-on-a-chip. This figure is created via BioRender with credit. ECM, extracellular matrix; EGF, epidermal growth factor; FGF7, fibroblast growth factor 7; FGF10, fibroblast growth factor 10; ALI, air-liquid interface; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; PD-1, programmed cell death protein 1; PD-L1, programmed cell death-ligand protein 1; PDO, patient-derived organoid.