Applications and perspectives of tumor organoids in radiobiology (Review)

Abstract

Radiotherapy exhibits significant versatility and efficacy in cancer treatment, thereby playing a crucial role in the field of oncology. However, there remains an urgent need for extensive research on various aspects of radiotherapy, including target selection, damage repair and its combination with immunotherapy. Particularly, the development of in vitro models to replicate in vivo tumor lesion responses is vital. The present study provides a thorough review of the establishment and application of tumor organoids in radiotherapy, aiming to explore their potential impact on cancer treatment.

Keywords: applications; immunotherapy; perspectives; radiotherapy; tumor organoids.

Figure 1.

Evolutionary timeline of organoid development (2009–2023). A comprehensive timeline of organoid development from 2009 to 2023 highlighting the key milestones, including the introduction of colorectal carcinoma organoids in 2009, glioblastoma organoids in 2019, cardioids in 2020, trophoblast organoids in 2021, bone marrow organoids in 2022 and organoids with an immune system in 2023. Lgr5, leucine-rich repeat-containing G protein-coupled receptor 5.

Figure 2.

Workflow of PDO generation, characterization and applications. PDO generation begins with the acquisition of tumor fragments via surgical resection or core needle biopsy. These are then dissociated and filtered into a single-cell suspension upon arrival at the laboratory. Cells are seeded in conditional medium using methods such as submerged Matrigel culture, microfluidic 3D culture or air-liquid interface. Subsequently, PDOs are processed for cryopreservation to establish a patient biobank and subjected to morphological assays, including H&E/IHC/IF, DNA/RNA analysis, coupled with irradiation, drug tests, phase-contrast imaging and growth kinetics. A special focus is placed on neoadjuvant therapies such as radiochemotherapy and radiotherapy combined with immunotherapy, aimed at reducing tumor size, alleviating symptoms or improving surgical outcomes. Finally, experimental results are applied to patients for precision medicine. PDO, patient-derived organoid; H&E, hematoxylin and eosin; IHC, immunohistochemistry; IF, immunofluorescence.