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2015
Journal Article
Titel
A 3D human lung tumor test system on an acellular scaffold: Simulation of a biomarker-guided therapy
Titel Supplements
Abstract
Abstract
Lung cancer is often diagnosed late after the appearance of clinical symptoms, which implies that drugs for Non-Small Cell Lung Cancer treatment must be efficient to counteract tumors of advanced stages. Therefore, tumor models are required which reflect the clinical situation and allow a reliable drug testing. In the present study, we introduced a 3D human lung tumor model developed on the basis of a decellularized porcine jejunum. In order to simulate the approach of personalized medicine, we used either a human cell line with an activating EGFR mutation (HCC827) or EGFR wild-type cell lines (H441, A549). To block EGFR activation, we treated the tumor models with the EGFR inhibitor gefitinib: only in HCC827 cell proliferation was inhibited and apoptosis was induced, while in H441 and A549 cells, gefitinib treatment had no substantial effect. This correlates with the situation in the clinic as EGFR inhibitors have an effect only in patients with an EGFR mutation. Often, these patients that are sensitive to tyrosine kinase inhibitors (TKIs) develop a resistance to EGFR-TKI. Therefore, we established a gefitinib resistant cell line, which proliferates also under gefitinib treatment. To come closer to the in vivo conditions, we cultured our models dynamically in a bioreactor: a constant media flow was applied which enabled better nutrient supply and led to higher cell densities on the matrix mimicking tissue-like morphologies. Thus, our models are promising tools to investigating the efficacy of new substances, the mechanisms of resistance, and the signaling pathways involved.