Gene

Genetic heterogeneity

Cell biology

Organoid

Cisplatin

Biology

Paclitaxel

Cancer research

Drug

Computational biology

Pharmacogenomics

Genetics

Bioinformatics

Precision medicine

Drug response

Carboplatin

Internal medicine

Efficacy

Pharmacology

Chemotherapy

Oncology

Medicine

Ovarian cancer

Personalized medicine

Cancer

Phenotype

Pathology

Cell Reports

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.

Patient-Derived Ovarian Cancer Organoids Mimic Clinical Response and Exhibit Heterogeneous Inter- and Intrapatient Drug Responses