Abstract
Malignant pleural mesothelioma (MPM) is a rare and highly aggressive tumour that is associated with asbestos exposure. Due to its non-specific presenting symptoms and the need for imaging and tissue biopsies, diagnosis of MPM is delayed, thereby negatively impacting prognosis. Moreover, relapse from current treatments (chemotherapy, immunotherapy) is inevitable, making it palliative in intention. There is thus an urgent need for both earlier diagnosis and detection of chemotherapy resistance to improve patients' quality of life. Therefore, in this project, I aim to construct a diagnostic and a follow-up biomarker panel based on MPM-specific molecular alterations (copy number alterations (CNAs) and differentially methylated CpG sites) that can be detected in liquid biopsies. I already successfully established a patient-derived organoid model, which will be further optimised during this project. This model will eventually be used to detect genomic and methylomic alterations associated with chemotherapy resistance. Then, using a novel highly sensitive detection technique, the two biomarker panels will be detected in circulating tumour DNA of liquid biopsies, enabling rapid and minimally invasive tumour detection. Consequently, the goal of this project is to improve early diagnosis as well as enable patient follow-up during chemotherapy, in order to reduce unnecessary toxicity and futile treatment.
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