Journal article
Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids to Predict Carboplatin Resistance
Biomedicines, Vol.9(8), 1021
08/16/2021
DOI: 10.3390/biomedicines9081021
PMCID: PMC8394135
PMID: 34440225
Abstract
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 EC
values were determined. One organoid line, UK1254, was predicted to be resistant to carboplatin based on its EC
value (50.2 µM) being above clinically achievable Cmax. UK1254 had a significantly shorter PFS than the rest of the subjects (
= 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.
Details
- Title: Subtitle
- Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids to Predict Carboplatin Resistance
- Creators
- Justin W Gorski - Albert B. Chandler HospitalZhuwei Zhang - Albert B. Chandler HospitalJ Robert McCorkle - University of KentuckyJodi M DeJohn - University of KentuckyChi Wang - Albert B. Chandler HospitalRachel W Miller - Albert B. Chandler HospitalHolly H Gallion - Albert B. Chandler HospitalCharles S Dietrich - Albert B. Chandler HospitalFrederick R Ueland - Albert B. Chandler HospitalJill M Kolesar - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Biomedicines, Vol.9(8), 1021
- DOI
- 10.3390/biomedicines9081021
- PMID
- 34440225
- PMCID
- PMC8394135
- ISSN
- 2227-9059
- eISSN
- 2227-9059
- Grant note
- T32 CA160003 / NCI NIH HHS P30CA177558 / Office of Research Infrastructure Programs, National Institutes of Health P30 CA177558 / NCI NIH HHS
- Language
- English
- Date published
- 08/16/2021
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695798902771
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