Oncogramme, an Adapted Method for Individualized Tumour Response Testing of Ovary Cancer Treatments
Giraud S, Croce S, Bessette B, Stoeckle E, Guyon F, Mac Grogan G, Floquet A, Velasco V, Mannina C, Lautrette C.
Ovarian cancer is the most lethal malignancy of the female reproductive tract. Up to now, initial treatment of advanced ovarian cancer is still based on complete surgical resection in association with chemotherapy but, most of the patients relapse. Choice of the best chemotherapeutic drugs remains difficult and uncertain. In this respect, individualized tumour response testing methods may help identifying the most suitable drug and individualizing molecule administration outside of the classical setting of chemotherapeutic lines. A new test with optimized processes was developed to achieve such a goal. Ovarian tumour fragments were dissociated and primary culture of the cells obtained was done following standardized processes and using a chemically-defined culture medium (OncoMiD for ovary). These ex vivo ovarian tumour models were characterized through pathological analyses performed on cells both from the tumour fragment of origin and the primary cultures. Proliferative rate of primary cells were determined by BrdU incorporation. After cell treatment with various chemotherapeutics, cytotoxicity was determined through detection of cell death using a calcein acetoxymethyl (AM) / ethidium homodimer (EthD) double labelling.
The defined medium allowed a 92% culture success rate, with proliferation of cultured ovarian tumour cells. Ex vivo ovarian tumour models obtained also maintained heterogeneity of cells found in patient's cancer tissue, while fibroblast colonization and survival of immune cells were both prevented. Moreover, cell death analysis provided for each tumour individual drug profiles termed Oncogramme, with statistically significant values. Oncogramme on human ovary tumour samples is an ex vivo method that can predict patient cell sensitivities to drugs. This test now needs to be validated through a phase I clinical trial.
Keywords: Ovary cancer; Primary culture; Chemotherapeutics; Therapy personalization