Organoid development in cancer genome discovery

Abstract

The tumor response to most therapeutic agents in cancer is highly unpredictable. Cancer models which can adequately represent tumor heterogeneity and predict in vivo drug sensitivity are intense areas of investigation. Cancer cell lines and patient-derived xenograft models are the most frequently used models in cancer research and anticancer drug screening. Recently, cancer 'organoid' culture conditions have been developed to establish in vitro growth of patient-derived samples at higher efficiency and they are very promising for large scale drug screening and fundamental cancer biology research. Here, we leverage our experience in prostate cancer to discuss the advantages and limitations of these cancer models and summarize the development of cancer organoid culture--a development which may provide a new path towards personalized medicine in the future.

Figure 1

Examples of mouse prostate organoid and human prostate cancer organoid. A. Mouse prostate organoid (phase contrast)(I), mouse prostate organoid (II) and mouse prostate gland (III) immunofluorescent staining with cytokeratin 5 positive basal cells (Red) and cytokeratin 8 positive luminal cells (Green). B. H&E of MSK-PCa1 in situ tumor (I′), MSK-PCa1 organoid (IT) and xenograft of MSK-PCa1 organoid (III′).

Figure 2

Schematic diagram of cancer organoid cultures and drug sensitivity test. Isolate prostate cancer cells from freshly collected tissue biopsies or circulating tumor cells; seed the tumor cells into prostate organoid culture system; analyze the organoid cell at the histological, genomic and transcriptomic level; compare with the original tumor; predict potential therapeutic drugs using the information from genomic and transcriptional analysis; test the drug sensitivity using the organoid models.