Identification of the most effective chemotherapy in recurrent ovarian cancer using the spheroid model

Background and aims: Most ovarian cancer patients suffer relapse despite multimodal treatment. According to international guidelines a variety of drug options exist. The aim of the present study was the identification of the most effective chemotherapy for the individual ovarian cancer patient using the spheroid model. Treatment response pattern was correlated with the cellular and molecular characteristics of the individual tumor.

Patients and methods: Spheroids were directly generated from fresh tumor tissues (n = 33) and tested for a variety of guideline recommended therapeutic options. Efficacy of the drugs was tested with the ATP assay. Tumor biology of the ovarian cancers was evaluated by immunohistochemistry and qPCR.

Results: Recurrent ovarian cancers were found equal (33%) or even more chemosensitive (54%) to carboplatin/gemcitabine (CG) treatment compared to carboplatin/paclitaxel (CP) therapy. Threosulfan, topotecan and vinorelbin also represented effective drugs depending on the individual cancer tissue. Comparison of different tumor locations of the same patients revealed striking differences in the drug response pattern. Drug resistance was mediated by various molecular biomarkers, such as FRANCF, CCND1, RAD50 and KIAA1430 expressed by the tumor cells. Interestingly, the cellular micro-milieu including a low fraction of tumor infiltrating lymphocytes and tumor associated macrophages had a strong impact on the drug response pattern.

Conclusion: The ovarian cancer spheroid model represents a promising tool to select the most effective chemotherapy for the individual cancer patient.