Research Nele De Meulenaere

Abstract

Pleural mesothelioma (PM) is a rare and highly aggressive tumor linked to asbestos exposure. Due to its non-specific presenting symptoms and the need for tissue biopsies, diagnosis of PM is delayed, negatively impacting prognosis. Moreover, PM treatment remains palliative due to chemo- and immunotherapy resistance. This emphasizes the need for earlier diagnosis and therapy resistance interception. This could improve patients' outcome, quality of life and even enable the possibility for new treatments. Therefore, in this project, I aim to tackle both late diagnosis and therapy resistance. First, I will construct a diagnostic and a predictive biomarker panel based on PM-specific molecular alterations (differentially methylated CpG sites and copy number alterations) that can be detected in liquid biopsies. The diagnostic biomarker panel is currently being validated. Using IMPRESS, our in-house developed detection technique, we will detect these biomarker panels in circulating tumor DNA, enabling rapid and minimally invasive tumor detection. Additionally, employing a multi-omics approach, I will identify molecular changes and dysregulated pathways associated with acquired chemo-immunotherapy resistance, in a unique patient cohort. These potential therapeutic targets can be used in further research on personalized treatments. Consequently, through this project, I aim to facilitate early diagnosis, minimize toxic side effects, and pave the way towards novel treatment options.

Researcher(s)

• Promoter: Op de Beeck Ken
• Co-promoter: Deben Christophe
• Co-promoter: Van Camp Guy
• Fellow: De Meulenaere Nele

Research team(s)

• Center for Oncological Research (CORE)

Project website

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Op de Beeck Ken
• Fellow: De Meulenaere Nele

Research team(s)

• Center for Oncological Research (CORE)

Project type(s)

• Research Project