In vitro drug testing using patient-derived ovarian cancer organoids

• Published in: Journal of ovarian research Vol. 17; no. 1; pp. 194 - 12
• Main Authors: Chen, Lin-Yu, Chou, Yu-Ting, Liew, Phui-Ly, Chu, Ling-Hui, Wen, Kuo-Chang, Lin, Shiou-Fu, Weng, Yu-Chun, Wang, Hui-Chen, Su, Po-Hsuan, Lai, Hung-Cheng
• Format: Journal Article
• Language: English
• Published: London BioMed Central 02.10.2024; BioMed Central Ltd; BMC
• Subjects: Aged; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Cancer; Cancer patients; Cervical cancer; Chemotherapy; Drug Screening Assays, Antitumor - methods; Drug testing; Drug therapy; Drugs; Female; Gynecology; Humans; Immunohistochemistry; Medicine; Medicine & Public Health; Middle Aged; Organoids - drug effects; Organoids - pathology; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Patient-derived organoids; Pharmaceutical industry; Precision medicine; Reproductive Medicine; Scientific equipment and supplies industry; Tumor proteins; United States; Patient-derived organoids; Precision medicine; Drug testing; Ovarian cancer
• ISSN: 1757-2215; 1757-2215
• DOI: 10.1186/s13048-024-01520-2

Background Ovarian cancer is the most lethal gynecological cancer. As the primary treatment, chemotherapy has a response rate of only 60–70% in advanced stages, and even lower as a second-line treatment. Despite guideline recommendations, which drugs will be most effective remains unclear. Thus, a strategy to prioritize chemotherapy options is urgently needed. Cancer organoids have recently emerged as a method for in vitro drug testing. However, limited clinical correlations have been assessed with test results from cancer organoids, particularly in gynecological cancers. We therefore aimed to generate patient-derived organoids (PDOs) of ovarian cancer, to assess their drug sensitivities and correlations with patient clinical outcomes. Methods PDOs were generated from fresh tumors obtained during surgical resection, which was then cultured under matrix gel and appropriate growth factors. Morphological and molecular characterization of PDOs were assessed by phase contrast microscopy and paraffin-embedded histopathology. Expressions of PAX8, TP53, WT1, CK7, and CK20 were tested by immunohistochemical staining and compared with parental tumor tissues and the human protein atlas database. PDOs were subjected to in vitro drug testing to determine drug sensitivity using Titer-Glo ® 3D Cell Viability Assay. PDO viability was measured, and area under the curve calculated, to compare responses to various compounds. Correlations were calculated between selected patients’ clinical outcomes and in vitro drug testing results. Results We established 31 PDOs. Among them, 28 PDOs can be expanded, including 15, 11, and 2 from ovarian, endometrial, and cervical cancers, respectively. The PDOs preserved the histopathological profiles of their originating tumors. In vitro drug testing of 10 ovarian cancer PDOs revealed individual differential responses to recommended drugs, and interpersonal heterogeneity in drug sensitivity, even with the same histology type. Among four patients who were platinum sensitive, resistant, or refractory, PDO drug responses correlated well with their clinical courses. Conclusion In vitro drug testing using ovarian cancer organoids is feasible and correlates well with patient clinical responses. These results may facilitate development of precision chemotherapy and personalized screening for repurposed or new drugs.