There remains an unmet need for preclinical models to enable personalized therapy for ovarian cancer (OC) patients. Here we evaluate the capacity of patient-derived organoids (PDOs) to predict clinical drug response and functional consequences of tumor heterogeneity. We included 36 whole-genome-characterized PDOs from 23 OC patients with known clinical histories. OC PDOs maintain the genomic features of the original tumor lesion and recapitulate patient response to neoadjuvant carboplatin/paclitaxel combination treatment. PDOs display inter-and intrapatient drug response heterogeneity to chemotherapy and targeted drugs, which can be partially explained by genetic aberrations. PDO drug screening identifies high responsiveness to at least one drug for 88% of patients. PDOs are valuable preclinical models that can provide insights into drug response for individual patients with OC, complementary to genetic testing. Generating PDOs of multiple tumor locations can improve clinical decision making and increase our knowledge of genetic and drug response heterogeneity.

The distribution pattern of a periportal enzyme (carbamoylphosphate synthetase) and a pericentral enzyme (glutamine synthetase) in human and rat liver has provided an objective parameter to delineate the zonal boundaries of the liver acinus. On sections, the pericental zone (zone 3) is circular and discrete rather than star-like and reticular, as predicted by the acinar concept, whereas the periportal zone (zone 1) is reticular, i.e. contiguous between adjacent acini rather than discrete. Three-dimensionally, the composite of pericentral zones (the pericentral compartment) follows the branching pattern of the terminal hepatic (central) vein, whereas the composite of periportal zones (the periportal compartment) envelops the pericentral compartment as a three-dimensional network (reticulum). This modified concept that is based upon the three-dimensional distribution of hepatocyte-specific enzymes is supported by data from the literature regarding the three-dimensional angioarchitecture of the liver, the perfusion pattern of the liver and the three-dimensional pattern of tissue oxygenation. Hence, a unified concept of the liver architecture that is based upon the observed distribution pattern of blood flow, of gene expression and of metabolism can be established.