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Review
, 8 (5)

Application of Cancer Organoid Model for Drug Screening and Personalized Therapy

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Review

Application of Cancer Organoid Model for Drug Screening and Personalized Therapy

Jumpei Kondo et al. Cells.

Abstract

Drug screening-i.e., testing the effects of a number of drugs in multiple cell lines-is used for drug discovery and development, and can also be performed to evaluate the heterogeneity of a disease entity. Notably, intertumoral heterogeneity is a large hurdle to overcome for establishing standard cancer treatment, necessitating disease models better than conventional established 2D cell lines for screening novel treatment candidates. In the present review, we outline recent progress regarding experimental cancer models having more physiological and clinical relevance for drug screening, which are important for the successful evaluation of cellular response to drugs. The review is particularly focused on drug screening using the cancer organoid model, which is emerging as a better physiological disease model than conventional established 2D cell lines. We also review the use of cancer organoids to examine intertumor and intratumor heterogeneity, and introduce the perspective of the clinical use of cancer organoids to enable precision medicine.

Keywords: cancer; cell lines; drug screening; heterogeneity; organoid; precision medicine; spheroid.

Conflict of interest statement

J.K. and M.I. belong to the department of clinical bio-resource research and development in Kyoto University, which is sponsored by KBBM.

Figures

Figure 1
Figure 1
Preparation of cancer stem-like cell (CSC)-derived organoids and cancer tissue-originated spheroids (CTOSs). In both methods, tumor specimens are mechanically and enzymatically digested. To generate CSC-derived organoids, tumor tissues are dispersed at the single-cell level, and organoid formation occurs by either re-aggregation or clonal proliferation. Optionally, incompletely dissociated fragments trapped by filters are further trypsinized to recover more single cells. In contrast, to generate CTOSs, tumor tissues are incompletely digested into fragments on purpose by milder conditions. These cell clusters rapidly form spherical-shaped CTOSs within 24 h. Because the cell-cell contact is retained during the preparation process, CTOS could better recover heterogenous cells including those at non-CSC state by avoiding anoikis, On the other hand, CSC-derived organoids could better enrich the cells with cancer-stem like property. However, it remains an open question whether the cells obtained by these different methods are interchangeable or not.

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