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

Int J Oncol. 2022 Oct;61(4):128. doi: 10.3892/ijo.2022.5418. Epub 2022 Sep 9.


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.

Keywords: drug sensitivity; ex vivo; ovarian cancer; type I and II.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Carcinoma, Ovarian Epithelial / drug therapy
  • Dasatinib / pharmacology
  • Dasatinib / therapeutic use
  • Drug Resistance
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Neoplasms, Glandular and Epithelial* / drug therapy
  • Ovarian Neoplasms* / pathology


  • Antineoplastic Agents
  • Dasatinib

Grant support

This study was supported by grants from the Swedish Cancer Society (no. 17 0661), the Uppsala-Örebro Regional Research Fund (no. RFR-228691) and the Lions Research Cancer Fund (no. 2014).