Patient-derived organoids: Transforming cancer research and personalized medicine
by Dr. Sushama R. Chaphalkar, PhD. · News-MedicalNew review highlights how mini-organs model tumor environments, enhance drug testing, and pave the way for personalized cancer treatments.
In a recent review published in Med, researchers explored the use of patient-derived organoids (PDOs), or lab-grown mini-organs, as powerful tools in cancer research. PDOs replicate the complexity of human tumors, allowing for advanced studies of the tumor microenvironment (TME) and serving as preclinical models for gene editing, molecular profiling, drug testing, and biomarker discovery—crucial for personalized treatment approaches.
Background
Organoids are 3D models derived from patient cells that offer an accurate representation of human tissue. Recently approved as alternative drug-testing methods, organoids hold potential to replace animal models, providing insights into TME interactions and patient-specific drug responses.
PDO models and tumor interaction
PDO co-culture models simulate interactions between cancer and immune cells, aiding the study of drug resistance and immunotherapy. Cancer-associated fibroblast (CAF)-PDO and endothelial cell (EC)-PDO co-cultures reveal how CAFs drive tumor progression and drug resistance, while ECs stimulate angiogenesis and inflammation.
Advanced culture techniques
Air-liquid interface (ALI) cultures
ALI supports 3D tumor cultures, maintaining functional immune cells that help assess immune checkpoint blockade (ICB) therapies, enhancing precision medicine.
Microfluidic cultures
This method sustains tumor and immune cells in dynamic environments, aiding high-throughput drug screening and personalized immunotherapy.
Organ-on-Chip (OoC)
OoC replicates tumor physiology using microfluidics, enabling the study of resistance mechanisms and drug responses.
Genetic and molecular insights
PDOs derived from stem cells are key in studying cancer heterogeneity, with gene editing tools targeting oncogenes and tumor progression markers. Molecular profiling of PDOs allows for the identification of tumor-specific mutations and biochemical dependencies, offering valuable insights beyond traditional biopsy limitations.
Drug screening and biomarkers
PDOs mimic patient-specific genetic diversity, assisting in drug response prediction and treatment guidance for resistant cancers.
Advances in spatial transcriptomics are enhancing high-throughput PDO-based drug screening. Additionally, PDOs aid in biomarker discovery, revealing treatment efficacy and mechanisms of drug resistance.
PDO biobanks
PDO biobanks, established for various cancers, support personalized therapy and drug research. While challenges remain, such as maturation and structural support, these biobanks have transformative potential in regenerative medicine and cancer treatment.
Conclusion
PDOs are physiologically relevant, high-throughput models for biomarker discovery, drug development, and personalized medicine.
With ongoing advancements in 3D culturing, gene editing, and computational tools, PDOs are poised to become essential, cost-effective resources in cancer care, paving the way for innovative, patient-specific therapies.
Journal reference:
- Tong, Le et al. (2024) Patient-derived organoids in precision cancer medicine. Med, 5 (11):1351–1377. doi: 10.1016/j.medj.2024.08.010. https://www.cell.com/med/fulltext/S2666-6340(24)00343-X