@conference{
author = "Stepanović, Ana and Dinić, Jelena and Podolski-Renić, Ana and Jovanović Stojanov, Sofija and Dragoj, Miodrag and Jovanović, Mirna and Lupšić, Ema and Milićević, Aleksandar and Glumac, Sofija and Marić, Dragana and Ercegovac, Maja and Pešić, Milica",
year = "2023",
abstract = "Introduction: Multidrug resistance (MDR) significantly hampers nonsmall cell lung carcinoma (NSCLC) drugs’ efficacy. To evaluate the contribution of MDR markers to anticancer drugs’ sensitivity, we performed pharmacological screening on patient-derived NSCLC cells ex vivo and assessed the expression of MDR markers in cancer and stromal (non-cancer) cells.
Material and Methods: Primary patient-derived cultures were established from the NSCLC resections. After short-term culturing (2-3 weeks), a mixed population of cancer and non-cancer cells were treated with 8 chemotherapeutics (cisplatin, carboplatin, paclitaxel, docetaxel, etoposide, vinorelbine, gemcitabine, and pemetrexed). The maximum concentration reached in human plasma to which the patient is exposed during therapy (Cmax) was set as an upper limit and four lower concentrations were
also applied during the study. Immunofluorescence assay enabling discrimination of epithelial cancer cells positive to a cocktail of antibodies against cytokeratin 8/18 vs. negative mesenchymal noncancer cells was conducted using high-content imager ImageXpress Pico (Molecular Devices) with CellReporterXpress 2.9 software. Within the same immunoassay, MDR markers (ABCB1, ABCC1, and ABCG2) were analyzed by corresponding antibodies.
Results and Discussions: Among all tested compounds, only gemcitabine increased the number of positive cancer cells to all MDR markers in all investigated primary cell cultures. Pemetrexed did not
change the number of MDR-positive cancer cells. In a patient sample IIIA stage bearing EGFR mutation
(L858R), the number of positive cancer cells to all MDR markers increased upon treatment with cisplatin, carboplatin, paclitaxel, docetaxel, etoposide, vinorelbine, and gemcitabine. Stromal (non-cancer) cells mainly followed the pattern of MDR observed in cancer cells.
Conclusion: Novel functional immunoassay can provide valuable information about the sensitivity of NSCLC to different drugs and possible treatment outcomes based on the
expression of MDR markers.",
publisher = "John Wiley and Sons Inc",
journal = "EACR 2023 Congress: Innovative Cancer Science; 2023 Jun 12-15; Torino, Italy",
title = "Novel functional immunoassay for identification of multidrug resistance markers in non-small cell lung carcinoma patient-derived cells",
doi = "10.1002/1878-0261.13469",
pages = "461-462"
}
