Application of Organoid Models in Prostate Cancer Research

Abstract

Complex heterogeneity is an important characteristic in the development of prostate cancer (PCa), which further leads to the failure of known therapeutic options. PCa research has been hampered by the current in vitro model systems that cannot fully reflect the biological characteristics and clinical diversity of PCa. The tumor organoid model in three-dimensional culture retains the heterogeneity of primary tumor tissues in vitro well and enables high-throughput screening and genome editing. Therefore, the establishment of a PCa organoid model that recapitulates the diverse heterogeneity observed in clinical settings is of great significance for the study of PCa. In this review, we summarize the culture conditions, establishments, and limitations of PCa organoids and further review their application for the study of pathogenesis, drug screening, mechanism of drug resistance, and individualized treatment for PCa. Additionally, we look forward to other potential developmental directions of PCa organoids, such as the interaction between prostate cancer tumor cells and their microenvironment, clinical individualized treatments, heterogeneous transformation model, tumor immunotherapy, and organoid models combined with liquid biopsy. Through this, we provide more effective preclinical experimental schemes using the PCa organoid model.

Defining the challenges and opportunities for using patient‐derived models in prostate cancer research

“…16 PDOs can overcome some of the limitations of PDXs, because they are more suitable for genetic engineering and high-throughput drug testing. 17 However, PDO are usually grown as monocultures lacking interaction between different cell types. PDEs are pieces of patient tissue that are maintained ex vivo, often suspended above culture media with filters or gelatin sponges.…”

Advances in the application of 3D tumor models in precision oncology and drug screening

“…Tumor organoids can be used to study the dynamic evolution of tumors and to perform preclinical efficacy evaluation, tumor microenvironment studies, and assessments of adjuvant immunotherapy. With the further development of organoid biobanks and chips, the future use of tumor organoid research is worth investigating during the development of preclinical experiments ( Tatullo et al, 2020 ; Benitez et al, 2021 ; Zhou et al, 2021 ).…”

Current status and clinical application of patient-derived tumor organoid model in kidney and prostate cancers

“…For example, PDTO systems can be used to study mechanisms of oncogenesis and anti-cancer drug resistance and to determine the origin of cancer cells. Furthermore, considering that cancer stem cells can contribute to resistance to chemotherapy and initiation of the process of cancer, PDTO can help us identify cancer stem cells initiating tumor that leads to resistance to anti-cancer drugs ( 10 , 13 ). In this context, PDTO platform opens up the opportunity to apply personalized medicine.…”

“…Moreover, prostate cancer cell line model does not reflect the heterogeneity of prostate cancer. For these reasons, prostate cancer organoid has been developed as a suitable model system to overcome these limitations ( 13 , 24 ). Prostate cancer organoids can recapitulate organ-like structures.…”

“…Here, we review the advantages of PDTO systems, particularly in kidney and prostate cancers. Table 1 summarize advantages and disadvantages of 2D culture, PDX, and PDTO systems ( 13 ).…”