In vitro drug testing using patient-derived ovarian cancer organoids.

Autor: Chen LY; Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan., Chou YT; Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan., Liew PL; Department of Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan.; Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan., Chu LH; Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan., Wen KC; Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan.; Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan., Lin SF; Department of Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan., Weng YC; Translational Epigenetics Center, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan., Wang HC; Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.; Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, 11490, Taiwan., Su PH; College of Health Technology, National Taipei University of Nursing and Health Sciences, Taipei, 11219, Taiwan., Lai HC; Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan. hclai30656@gmail.com.; Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan. hclai30656@gmail.com.; Translational Epigenetics Center, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan. hclai30656@gmail.com.; Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, 11490, Taiwan. hclai30656@gmail.com.
Jazyk: angličtina
Zdroj: Journal of ovarian research [J Ovarian Res] 2024 Oct 02; Vol. 17 (1), pp. 194. Date of Electronic Publication: 2024 Oct 02.
DOI: 10.1186/s13048-024-01520-2
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje