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Poster Display session (Friday) (ID 65)
- Event: ELCC 2018
- Type: Poster Display session
- Presentations: 1
- Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
64P - Cisplatin-resistant phenotype: Characterization, adaptation to EGFR signaling and sensitivity to EGFR inhibitors in NSCLC cells (ID 419)
12:30 - 13:00 | Author(s): R. Kiefl
The emergence of platinum resistance is a significant obstacle to clinical management of lung cancer. We aimed to analyze the EGFR signaling and efficacy of EGFR inhibitors in acquired cisplatin resistance. Better understanding forms a basis for the development of novel combination therapies that could enhance patient survival.
An isogenic clinical model was used to induce resistance in a panel of cell lines (H838, HCC827, H1975 and H1650 NSCLC cells) and H1339, an SCLC cell line. Cells were exposed to cisplatin (1 μg/ml/3 hrs/week) followed by recovery periods over of 4 weeks, and cisplatin–resistant phenotype (CRP) derived from original, age–matched naïve cells. They were then characterized by survival, proliferation, colony formation, and apoptosis. EGFR family receptors, phosphorylation and downstream signalling was assessed by EGFR phosphorylation and the PathScan Signaling array. The effects of EGFR TKIs (erlotinib, gefitinib, afatinib, and rociletinib) on CRP cells was evaluated at clinical concentrations.
CRP cells demonstrated increased survival, proliferation and resistance to apoptosis against the cisplatin challenge. CRP cells displayed altered expression of EGFR receptor family and their phosphorylation and critical nodes of signaling. But their appearance varied from cell line to cell line in comparison to their respective controls. The EGFR TKIs (except erlotinib on H838 cells) showed similar effects on CRP and their naïve cells.
Our results identified CRP of NSCLC cells, which exhibited enhanced total EGFR and Met protein expression and their phosphorylation. This altered the expression of critical oncoproteins. The information can be used to design combination therapies with other TKIs to improve patient life.
Clinical trial identification:
Legal entity responsible for the study:
Respiratory Medicine and Thoracic Oncology (LMU Klinikum der Universität München)
German Center for Lung Research (DZL), Germany
All authors have declared no conflicts of interest.
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