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Article

Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids to Predict Carboplatin Resistance

1
Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Kentucky Chandler Medical Center, 800 Rose Street, Lexington, KY 40536-0263, USA
2
Department of Cancer Biostatistics, University of Kentucky Chandler Medical Center, 800 Rose Street, Lexington, KY 40536-0263, USA
3
Department of Pharmacy Practice & Science, University of Kentucky College of Pharmacy, 540 Healthy Kentucky Research Building, 760 Press Avenue, Lexington, KY 40539-0596, USA
4
University of Kentucky College of Medicine, 800 Rose Street, MN150, Lexington, KY 40536-0298, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Beata Pajak and Anna Jaśkiewicz
Biomedicines 2021, 9(8), 1021; https://doi.org/10.3390/biomedicines9081021
Received: 29 June 2021 / Revised: 12 August 2021 / Accepted: 13 August 2021 / Published: 16 August 2021
(This article belongs to the Special Issue Killing It Softly–New Approaches to Overcome Cancer Chemoresistance)
The development of patient-derived tumor organoids (TOs) from an epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine. Here, we utilized TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high-grade, serous epithelial ovarian cancer tumor organoid lines from tissue obtained during debulking surgery (two neoadjuvant-carboplatin-exposed and four chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1, and 0.1 µM). Cell viability curves and resultant EC50 values were determined. One organoid line, UK1254, was predicted to be resistant to carboplatin based on its EC50 value (50.2 µM) being above clinically achievable Cmax. UK1254 had a significantly shorter PFS than the rest of the subjects (p = 0.0253) and was treated as a platinum-resistant recurrence. Subsequent gene expression analysis revealed extensively interconnected, differentially expressed pathways related to NF-kB, cellular differentiation (PRDM6 activation), and the linkage of B-cell receptor signaling to the PI3K–Akt signaling pathway (PI3KAP1 activation). This study demonstrates that patient-derived tumor organoids can be developed from patients at the time of primary or interval debulking surgery and may be used to predict clinical platinum sensitivity status or to investigate drivers of carboplatin resistance. View Full-Text
Keywords: ovarian cancer; tumor organoids; chemotherapy resistance; carboplatin; integrated genetic analysis ovarian cancer; tumor organoids; chemotherapy resistance; carboplatin; integrated genetic analysis
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MDPI and ACS Style

Gorski, J.W.; Zhang, Z.; McCorkle, J.R.; DeJohn, J.M.; Wang, C.; Miller, R.W.; Gallion, H.H.; Dietrich, C.S.; Ueland, F.R.; Kolesar, J.M. Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids to Predict Carboplatin Resistance. Biomedicines 2021, 9, 1021. https://doi.org/10.3390/biomedicines9081021

AMA Style

Gorski JW, Zhang Z, McCorkle JR, DeJohn JM, Wang C, Miller RW, Gallion HH, Dietrich CS, Ueland FR, Kolesar JM. Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids to Predict Carboplatin Resistance. Biomedicines. 2021; 9(8):1021. https://doi.org/10.3390/biomedicines9081021

Chicago/Turabian Style

Gorski, Justin W., Zhuwei Zhang, J. R. McCorkle, Jodi M. DeJohn, Chi Wang, Rachel W. Miller, Holly H. Gallion, Charles S. Dietrich, Frederick R. Ueland, and Jill M. Kolesar. 2021. "Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids to Predict Carboplatin Resistance" Biomedicines 9, no. 8: 1021. https://doi.org/10.3390/biomedicines9081021

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