Breast cancer organoids: Advancements and applications in precision medicine

Global burden of breast cancer, highlighted by increasing incidence and mortality rate, remains an unmet clinical challenge. The mounting need of cancer drug development is, however, often impeded by translation discordance of preclinical success. Traditional research tools, including monolayer cell lines and animal models, fail to reflect both the inter- and intra-tumoral heterogeneous nature of cancer, which is a prominent feature of breast cancer. Patient-derived organoids, instead, hold significant promise in revolutionizing cancer research. Organoids are three-dimensional, multicellular tissue cultures formed by stem cells through self-organization. They have emerged as powerful research tools given their faithful recapitulation of cellular architecture and genetic diversity of the original tissues. Comprehensive molecular characterization has revealed high concordance of gene and protein signatures between the parental tumors and the organoids. Organoids have therefore demonstrated to be a reliable predictive platform for drug sensitivity testing in identifying actionable targets and expediting drug discovery. Recent biological and bioengineering advancements further highlight the unique versality and the expanding complexity of organoid-based cultures. PDX (Patient-derived xenografts)-derived organoids, co-culture with niche components, assembloids and organoid-on-chip are amongst some of the key innovations. These inventions also mitigated some of the limitations with organoid cultures including the lack of microenvironment and vascularization. With the development of organoid technology and establishment of patient-derived organoid biobanks, organoids have opened up exciting avenues in biomedical research in the studies of development, physiology and diseases. Future development addressing drawbacks associated with current organoid cultures is warranted and will maximize their clinical impact in precision medicine.