The search for new treatment strategies for malignant pleural mesothelioma

Leiden Repository

The search for new treatment strategies for malignant pleural mesothelioma

Type: Doctoral Thesis
Title: The search for new treatment strategies for malignant pleural mesothelioma
Author: Schunselaar, L.M.
Issue Date: 2019-01-15
Keywords: Malignant pleural mesothelioma
Personalized treatment
FGFR
5T4
BAP1
Abstract: Malignant pleural mesothelioma (MPM) is an aggressive tumor of the mesothelial cells lining the pleura. The poor prognosis of patients indicates the importance to find more effective treatments. Therefore, this thesis focused on finding new treatment strategies for MPM. We present a method in which primary MPM cultures were chemically profiled to determine second-line treatment for patients. With this personalized treatment strategy we were able to predict individual patient responses to selected drugs. Based on the chemical profiles of all tumor cultures, these cultures could be divided in three groups. Transcriptomic analysis of these groups identified a unique genetic profile separating these groups and identifying the fibroblast growth factor receptor (FGFR) as a new target for the treatment of MPM. The cultures sensitive to FGFR inhibitors were dependent on FGFR3 mediated signaling which was regulated by BAP1, indicating BAP1 can serve as a biomarker for this treatment. Another target explored in this thesis was 5T4. We showed that 5T4 was only expressed in the tumor cells and that antibody-drug conjugates effectively kill high 5T4 expressing MPM cells. Altogether we present different promising novel strategies in the treatment of MPM, which could improve the survival outcome of these patients. 
Promotor: Supervisor: Neefjes J.J.C., Baas P. Co-Supervisor: Zwart W.
Faculty: Medicine / Leiden University Medical Center (LUMC)
University: Leiden
Uri: urn:isbn:9789463234481
Handle: http://hdl.handle.net/1887/67915
 

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