Tumor organoids in translational cancer research: Models for personalized therapy

Table 1 Tumor organoid applications in drug screening

Cancer type	Drug tested	Organoid response	Clinical relevance
Colorectal	5-fluorouracil	Organoids responded well, mimicking patient responses	High
Ovarian	Platinum-based chemo	Identified platinum-resistant populations	High
Lung	EGFR inhibitors	EGFR-mutant organoids sensitive to inhibitors	Moderate

Table 2 Comparative analysis of tumor organoids, patient-derived samples, and 2D cell lines

Aspect	Tumor organoids	Patient-derived samples	2D cell lines
Biological relevance	Highly relevant; mimics tumor architecture, heterogeneity, and microenvironment	Most relevant; directly from the patient, includes tumor's genetic and epigenetic features	Less relevant; lacks 3D structure, tumor heterogeneity, and microenvironment
Scalability	Scalable to some extent but limited by culture complexity and maintenance	Limited scalability; fresh samples are often hard to obtain and maintain	Highly scalable; easy to culture and propagate for large-scale studies
Cost	Expensive due to specialized culture requirements, patient-specific nature, and maintenance	Expensive; obtaining and maintaining fresh tumor samples can be costly	Least expensive; widely available, easy to maintain with basic culture conditions
Reproducibility	Can have variability due to culture conditions, patient heterogeneity, and protocol differences	Reproducibility can vary, especially with ex vivo cultures or expansion	Highly reproducible; easy to maintain and culture with consistent results
Genetic and epigenetic stability	Risk of epigenetic drift, clonal evolution, and gene expression changes during long-term culture	Directly reflects the genetic makeup of the patient's tumor, but cannot be cultured long-term	May not represent the genetic variability or epigenetic features of patient tumors
Use case	Ideal for personalized medicine, drug screening, and modeling complex tumor microenvironments	Best for authentic tumor representation but limited by availability and culture challenges	Suitable for high-throughput screening, basic research, and testing in simpler contexts

Table 3 limitations and challenges associated with tumor organoid models

Limitation	Impact on organoid research	Potential solutions
Genetic and epigenetic instability	Affects long-term fidelity of organoid models	Develop protocols for standardization and stability
Lack of tumor microenvironment elements	Limits accurate modeling of immune responses and drug delivery	Incorporate immune cells and vascularization
Use of animal-derived matrices	Ethical concerns and variability in results	Develop animal-free matrices and standardized protocols