Figure 3.

Organoids can help study cancer heterogeneity and evolution. Cancer heterogeneity exists patient to patient (‘interpatient’) and within the same patient between different metastatic sites, as a function of time during treatment course, and even within regions of the same tumor site (‘intrapatient’). Such heterogeneity can be modeled by generating organoids from single cells that can each be grown as subclones that model a tumor cell population within the patient. On the other hand, growing organoids in bulk from tumors may reflect the overall behavior and response of a tumor as a whole and preserve key subclone‒subclone interactions and overall tumor clonal architecture. Circulating tumor cells often travel as single cells that can be grown in bulk conditions or grown as subclones without the need for cell separation. In either case, organoids can provide valuable and clinically applicable information regarding therapy response at the clonal level, though this tendency of tumor cells (and thus organoids derived from them) to be heterogeneous must be kept in mind when interpreting results. For example, in the hypothetical plot, the yellow subclone is responsive to therapy, whereas the orange subclone continues to grow.