Lung cancer is the leading cause of cancer death in the Netherlands. For years chemotherapy was the only (palliative) treatment, with a short survival of only months. Since the introduction of... Show moreLung cancer is the leading cause of cancer death in the Netherlands. For years chemotherapy was the only (palliative) treatment, with a short survival of only months. Since the introduction of immunotherapy in 2015, this survival has increased significantly, with the first results showing a survival of even a few years. However, the response rate is relatively low, the treatment is expensive and the (low percentage of) side effects are severe. Therefore a biomarker is needed to predict which patients would benefit of immunotherapy.This thesis is about the search for a new biomarker. With the use of the RNA of platelets, proteins, tumor markers in blood and a an electronic nose for exhaled breath, we tried to find a non-invasive biomarker for the prediction of response on immunotherapy and for the (future) use in clinical practice, some of which are promising. Show less
Ewing sarcoma is an aggressive primary malignant bone tumor with high degree of tumor vascularization and is the second most common sarcoma of bone in children and young adults. Patients... Show more Ewing sarcoma is an aggressive primary malignant bone tumor with high degree of tumor vascularization and is the second most common sarcoma of bone in children and young adults. Patients with disseminated disease at diagnosis or early relapse have a poor prognosis. To identify novel therapies and biomarkers for these patients we focused on the chemokines and chemokine receptors in Ewing sarcoma cells and their role its tumor microenvironment. CCL21 CXCL14, CXCR7 and the ratio between CXCR4-1 and CXCR4-2 have been identified as candidate prognostic markers, CCL21 immunotherapy as potential therapy and CXCR4 as potential therapeutic target in EWS. In addition, the presented peptide-based life cell imaging methods improve the ability to study CXCR4 cell membrane expression and dynamics qualitatively and quantitatively. This approach might be helpful for the measurement of anti-CXCR4 therapy efficacy. This work identified specific the chemokine signaling pathways that can be used to target Ewing sarcoma and its tumor microenvironment. Show less
Kelderman, S.; Heemskerk, B.; Tinteren, H. van; Brom, R.R.H. van den; Hospers, G.A.P.; Eertwegh, A.J.M. van den; ... ; Blank, C.U. 2014