Table 1.

Overview of the current sources to generate and culture in vitro cancer spheroids and organoids; advantages and inconvenience.

Cell Sources	Advantages	Inconvenience
Cancer cell lines	Readily available and can be purchased from various sources Low cost Easy to cultivate and maintain Can be used in high-throughput screens to identify new therapeutic targets and drug candidates	Not representative of tumor heterogeneity May not represent the in vivo microenvironment Can acquire genetic and epigenetic changes over time and may not reflect the original tumoral cell
Primary cells	Closer representation of the in vivo microenvironment of the patient’s tumor. More accurate reflection of the genetic and molecular changes that occur in the patient’s tumor Useful to test the effects of drugs and other therapies on the patient’s tumor (personalized medicine)	Difficult to obtain, especially for certain types of tumors Challenging to culture and maintain in the lab, especially for certain types of cells May not be representative of all patients, since each patient’s tumor is unique
Genetically modified cells	Study of specific genetic pathways or specific mutations that are found in a patient’s tumor	Not replicate the complexity of the in vivo microenvironment Not representative of tumor heterogeneity Not representative of the genetic diversity of the tumoral cells
Pluripotent stem cells	Organoids generation by differentiating them into cells that are similar to those found in a patient’s tumor Can be used to study the effects of genetic changes on tumor development Can provide a large number of cells for research	Technically challenging to differentiate into the specific cell types found in a patient’s tumor Not fully replicate the complexity of the in vivo microenvironment Not representative of tumor heterogeneity
Mixture of different cell sources	Better representation of the tumor microenvironment Study of the interactions between different cell types in the microenvironment Provide insights into the mechanisms of tumor progression and response to therapy. Can be used in high-throughput screens to identify new therapeutic targets and drug candidates	More difficult and complex to culture and study More difficult to scale up than those made from a single cell type, which can limit their use in high-throughput screens and other applications Not fully represent the complexity of the tumor microenvironment
Organoids including immune cells	Closely mimic the complex interactions between cancer cells and the immune system that occur in vivo Can provide important insights into the mechanisms of immune response and resistance Can be used in personalized immunotherapy applications Can be used to identify new therapeutic targets and drug candidates that modulate the immune response	It is challenging to include and maintain immune cells that are present in vivo More complex to culture and study More difficult to scale up than those made from a single cell type, which can limit their use in high-throughput screens and other applications