Table 1.

Advantages and disadvantages of pre-clinical models.

Model System	Advantages	Disadvantages
Cell lines	-Cost effective, quick timeline -Easily reproducible and have a consistent sample	-Exist in a 2D monolayer culture and fail to capture the 3D tumor microenvironment
Cell line xenografts	-Cost effective, quick timeline -Cell lines can be genetically manipulated making them ideal for target validation	-Fail to capture molecular diversity of tumors -Genetic aberrations can be due to cell line adaptation to in vitro growth conditions -Mice are immune-deficient so there is no way to study the interactions with the immune system -Tumor microenvironment is made of mouse stromal tissue
Patient derived xenografts	-Preserve tumor’s genomic characteristics -Some correlation between preclinical efficacy and clinical data -Helpful for studying drug resistance mechanisms	-Labor intensive and require access to surgical specimens -Extended timeline needed -Mice are immune-deficient so there is no way to study the interactions with the immune system -Tumor microenvironment is made of mouse stromal tissue
Genetically engineered mouse models	-Tumor arises from the tissue of origin (e.g., colon cancer arises from the colon rather than be implanted into the subcutaneous tissue) -Primary genetic defects are known -Helpful for studying different stages of a disease -Mouse has an immune system	-Extended timeline needed -Key biological differences between mouse and human cancer development (e.g., tumor suppressor mechanisms) -Useful for target validation, but not necessarily predictive of efficacy in clinical setting
Organoids	-3D structural, functional, and molecular similarity to the original tumor -Better represents the native tumor tissue -Correlate with clinical outcomes	-Often lack stromal tissue, blood vessels, and immune cells (although some studies are working to improve this)