2D cancer models — the classic cells in a dish — and animal models of cancer have long histories, but both have limitations in terms of their relevance to human cancer and their ability to replicate all the features of diseases.
Fortunately, new technologies are enabling a better way. Cancer spheroids are an up-and-coming group of models with increasing uses in research, including CRISPR screens. The combination of CRISPR screening and innovative bulk spheroid production techniques holds great promise for cancer research.
Scalable Cancer-Spheroid Models Can Lead to New Breakthroughs
Both spheroids and organoids are 3D culture models. Spheroids are aggregated masses of cells without polarity and usually with only one cell type. Organoids are often polarized, may contain a hollow lumen, and may contain a more complex mixture of cell types. These model systems allow researchers to study cancer and other diseases in a more physiologically relevant setting while lessening the reliance on model animals such as mice, whose biology has important differences from human biology.
While simpler to make than organoids, cancer spheroids can capture several aspects of tumor biology that 2D cultures don't replicate. For example, cells on the surface of a spheroid experience different microenvironments than those on the interior, effectively modeling the gradients of oxygen, drug, and nutrient availability in a real tumor. Cells in spheroids experience a closer match to the biophysical environment in a tumor since multiple aspects of cell-cell interactions and signaling differ in 2D versus 3D. Spheroids can also provide a better model for the gene expression and metabolic profile of in vivo tumors.
Bulk spheroid production can be a limiting factor in experiments, especially because uniformity is needed. However, recent technological developments allow researchers to grow spheroids reliably and with straightforward procedures.