Chemotherapy sensitivity testing on ovarian cancer cells isolated from malignant ascites

Abstract

Background: In epithelial ovarian cancer (EOC), 15-20% of the tumors do not respond to first-line chemotherapy (paclitaxel with platinum-based therapy), and in recurrences this number increases. Our aim is to determine the feasibility of cell proliferation assays of tumor cells isolated from malignant ascites to predict in vitro chemotherapy sensitivity, and to correlate these results with clinical outcome.Materials and Methods: Ascites was collected from twenty women with advanced EOC. Cell samples were enriched for tumor cells and EOC origin was confirmed by intracellular staining of CK7, surface staining of CA125 and EpCAM, and HE4 gene expression. In vitro sensitivity to chemotherapy was determined in cell proliferation assays using intracellular ATP content as an indirect measure of cell number. In vitro drug response was quantified by calculation of the drug concentration at which cell growth was inhibited with 50%. Clinical outcome was determined using posttreatment CA125 level.Results: Cell samples of twenty patients were collected, of which three samples that failed to proliferate were excluded in the analysis (15%). Three other samples were excluded, because clinical outcome could not be determined correctly. In twelve of the fourteen remaining cases (86%) in vitro drug sensitivity and clinical outcome corresponded, while in two samples (14%) there was no correspondence.Conclusions: Our study demonstrates the feasibility of drug sensitivity tests using tumor cells isolated from ascites of advanced EOC patients. Larger observational studies are required to confirm the correlation between the in vitro sensitivity and clinical outcome.

ZEB2 facilitates peritoneal metastasis by regulating the invasiveness and tumorigenesis of cancer stem-like cells in high-grade serous ovarian cancers

“…Expression of the ovarian cancer markers carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4) was determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses. Similar to a previous study [ 22 , 23 ], cells from ascites expressed either CA125 or HE4, while human skin fibroblasts (HSFs) did not express these markers (Fig. S1 A, B), indicating that the cells collected following our protocol were indeed ovarian cancer cells.…”

EM-transcriptomic signature predicts drug response in advanced stages of high-grade serous ovarian carcinoma based on ascites-derived primary cultures

“…In addition, the feasibility of chemoresistance tests in ascites cultures has been demonstrated ( den Ouden et al, 2020 ). Unlike other studies, we are the first to comprehensively analyze the hub genes related to EM and drug resistance in CIS/DOX-treated and untreated AS cultures at the transcriptional level.…”

Chemoresistance in Ovarian Cancer: The Role of Malignant Ascites

“…Recently, Velletri et al used ovarian cancer clinical samples across primary tumours and metastatic sites and demonstrated that MA-derived organoids retain key subpopulations and recapitulate features of the original samples acting as 'patient-matched avatars' that can be used in a precision oncology platform (117,118). Moreover, other groups have demonstrated the capacity for growing tumor cells from MA in vitro for drug sensitivity testing (106,119) and predicting clinical responses to therapy through assessment of biomarkers present in MA tumor cells (32,120,121). A study by Bi et al demonstrated that PDOs can be established in a high percentage of cases to perform drug tests in a timely manner and that PDOs have the potential to identify more efficient regiments (106).…”