Breast Cancer Organoids Model Patient-Specific Response to Drug Treatment

SIMPLE SUMMARY: The possibility to generate in the laboratory faithful models of patients’ tumors is of primary importance to capture cancer complexity and study therapy response in a personalized setting. Tumor organoids are 3D cell cultures, obtained from patients’ tumor tissues, that recapitulate several characteristics of the original tumor, thus representing a clinically relevant patient avatar. This study reports the generation and the molecular characterization of patient-derived organoids from invasive breast carcinomas. Our results proved the usefulness of these cancer models for designing patient-specific therapeutic approaches to treat highly aggressive cancers, but also highlighted the need to further improve this methodology to overcome its current limitations. ABSTRACT: Tumor organoids are tridimensional cell culture systems that are generated in vitro from surgically resected patients’ tumors. They can be propagated in culture maintaining several features of the tumor of origin, including cellular and genetic heterogeneity, thus representing a promising tool for precision cancer medicine. Here, we established patient-derived tumor organoids (PDOs) from different breast cancer subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple negative). The established model systems showed histological and genomic concordance with parental tumors. However, in PDOs, the ratio of diverse cell populations was frequently different from that originally observed in parental tumors. We showed that tumor organoids represent a valuable system to test the efficacy of standard therapeutic treatments and to identify drug resistant populations within tumors. We also report that inhibitors of mechanosignaling and of Yes-associated protein 1 (YAP) activation can restore chemosensitivity in drug resistant tumor organoids.