<em>Ex vivo</em> assessment of cancer drug sensitivity in epithelial ovarian cancer and its association with histopathological type, treatment history and clinical outcome

Bjersand,Kathrine; Blom,Kristin; Poromaa,Inger Sundström; Stålberg,Karin; Lejon,Ann-Marie; Bäckman,Fatma; Nyberg,Åsa; Andersson,Claes; Larsson,Rolf; Nygren,Peter

doi:10.3892/ijo.2022.5418

Ex vivo assessment of cancer drug sensitivity in epithelial ovarian cancer and its association with histopathological type, treatment history and clinical outcome

Authors:
- Kathrine Bjersand
- Kristin Blom
- Inger Sundström Poromaa
- Karin Stålberg
- Ann-Marie Lejon
- Fatma Bäckman
- Åsa Nyberg
- Claes Andersson
- Rolf Larsson
- Peter Nygren
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Affiliations: Department of Women's and Children's Health, Uppsala University, S‑751 85 Uppsala, Sweden, Department of Medical Sciences, Uppsala University, S‑751 85 Uppsala, Sweden, Department of Medical Sciences, Örebro University Hospital, S‑701 85 Örebro, Sweden, Department of Gynecology, Falun Hospital, S‑791 31 Falun, Sweden, Department of Immunology, Genetics and Pathology, Uppsala University, S‑751 85 Uppsala, Sweden
Published online on: September 8, 2022 https://doi.org/10.3892/ijo.2022.5418
Article Number: 128
Copyright: © Bjersand et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Epithelial ovarian cancer (EOC) is divided into type I and type II based on histopathological features. Type I is clinically more indolent, but also less sensitive to chemotherapy, compared with type II. The basis for this difference is not fully clarified. The present study investigated the pattern of drug activity in type I and type II EOC for standard cytotoxic drugs and recently introduced tyrosine kinase inhibitors (TKIs), and assessed the association with treatment history and clinical outcome. Isolated EOC tumor cells obtained at surgery were investigated for their sensitivity to seven standard cytotoxic drugs and nine TKIs using a short‑term fluorescent microculture cytotoxicity assay (FMCA). Drug activity was compared with respect to EOC subtype, preoperative chemotherapy, cross‑resistance and association with progression‑free survival (PFS). Out of 128 EOC samples, 120 samples, including 21 type I and 99 type II, were successfully analyzed using FMCA. Patients with EOC type I had a significantly longer PFS time than patients with EOC type II (P=0.01). In line with clinical experience, EOC type I samples were generally more resistant than type II samples to both standard cytotoxic drugs and the TKIs, reaching statistical significance for cisplatin (P=0.03) and dasatinib (P=0.002). A similar pattern was noted in samples from patients treated with chemotherapy prior to surgery compared with treatment‑naive samples, reaching statistical significance for fluorouracil, irinotecan, dasatinib and nintedanib (all P<0.05). PFS time gradually shortened with increasing degree of drug resistance. Cross‑resistance between drugs was in most cases statistically significant yet moderate in degree (r<0.5). The clinically observed relative drug resistance of EOC type I, as well as in patients previously treated, is at least partly due to mechanisms in the tumor cells. These mechanisms seemingly also encompass kinase inhibitors. Ex vivo assessment of drug activity is suggested to have a role in the optimization of drug therapy in EOC.

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