Single-cell transcriptome analysis of patient-derived organoids captures inter- and intratumor heterogeneity and uncovers targetable pathways in high grade serous ovarian cancer

PDOs maintain the inter- and intra-tumoral cellular heterogeneity of HGSOC. Chemotherapy targets proliferative cell subclusters, sparing non-proliferative ones. Dependency on OXPHOS represents an actionable vulnerability in PDOs, which can be exploited to hijack chemoresistance. Sequential chemotherapy and immunotherapy may also improve clinical response of HGSOC patients.