Karen Zwaenepoel associate professor

Research Karen Zwaenepoel

Research team

Development of the meCUP DNA-methylation test to improve the diagnosis of cancer of unknown primary using tissue and liquid biopsies. 01/11/2024 - 31/10/2028

Abstract

Currently, 3 to 5% of cancer patients receive a diagnosis of Cancer of Unknown Primary (CUP), where the tissue-of-origin remains unidentified. This uncertainty contributes significantly to patient anxiety and diminishes quality of life. Treatment options are limited to empiric chemotherapy, with median survival ranging from 6 to 9 months. Therefore, there is an urgent need for a novel test to accurately determine the tissue-of-origin in CUP. This project aims to develop, optimize, validate, and implement a rapid, cost-effective test known as meCUP for precise CUP diagnosis. Initially, we will create a comprehensive DNA methylation reference atlas. Subsequently, we will model and optimize the meCUP test, validating it with biobanked samples from patients with cancers of known and unknown primary origin. Following assay optimization and validation, a non-interventional prospective trial will assess the meCUP test's integration into diagnostic workflows, supporting future interventional clinical trials. Throughout the project, we will promote awareness of CUP to enhance access to the meCUP assay for patients in Belgium. We will also identify the specific needs and concerns of CUP patients to establish a dedicated care pathway. The meCUP project holds the potential to significantly enhance CUP diagnosis by offering a more accurate, accessible, and cost-effective method for identifying the primary tumor site. This advancement could improve treatment strategies, outcomes, and overall quality of life for CUP patients.

Researcher(s)

Research team(s)

Funding

  • PRIVE - non profit

Project type(s)

  • Research Project

Improving oral cancer surgery by intra-operative assessment of resection margins. 01/06/2024 - 31/05/2028

Abstract

Surgery is the mainstay of treatment for oral cavity squamous cell carcinoma (OCSCC). Adequate resection margins (i.e. a minimum distance of 5 mm between the tumor and the surface of the resection specimen) are crucial for local disease control and prognosis. Inadequate tumor resection necessitates adjuvant (chemo) radiation or re-operation. Despite such adjuvant treatment the prospects of the patient are definitely diminished by inadequate margins. In addition, both radiation and chemotherapy may significantly affect the decreased quality of life. Unfortunately, the current rate of adequate OCSCC surgical results is only 15%. Clearly, the combination visual inspection and palpation with pre-operative imaging (e.g. CT, MRI), is insufficient to warrant adequate resections. To compensate this, a common intraoperative procedure for surgeons is to take tissue samples from the surgical wound bed for intraoperative pathological assessment of the resection margin. However, this so called frozen section procedure has many limitations; only a small proportion of the resection margin can be inspected in this way and the samples may not be representative. Moreover, here is no measurement of margin length, so close margins cannot be detected. More importantly, frozen section of the wound bed has not been unambiguously demonstrated to improve outcome. Intraoperative assessment of resection margins (IOARM) of OCSCC resection specimen has been proven to be the way forward. This approach has led to an immediate increase in the number of adequate resections from 15% to more than 50%. However, it is not realistic to expect that such laborious intraoperative assessment requiring a well-trained dedicated team of specialists can be widely adopted to become a standard of care. Therefore, an objective easy-to-use technique is needed, to accurately assess all resection margins intraoperatively. In this project, we propose the development of such a technique based on Raman spectroscopy. Raman spectroscopy is a non-destructive optical technique, which provides detailed information of the biochemical composition of a tissue, without the use of labels, dyes or reagents. Because malignant transformation is associated with changes in the biochemical composition of tissues, Raman spectroscopy can be used to distinguish a normal tissue from tumor. Recently, we have clearly shown that tissue water content is a powerful biomarker for discrimination between OCSCC and uninvolved oral structures. We have found the water concentration in OCSCC to be consistently higher than in the surrounding tissue. This new finding opens the way to new opportunities in intraoperative assessment of resection margins, in an objective and time-efficient manner.

Researcher(s)

Research team(s)

Funding

  • PRIVE - non profit

Project type(s)

  • Research Project

Urine as a liquid biopsy for early stage cancer detection. 01/01/2020 - 31/12/2023

Abstract

Today, most cancers are diagnosed through tactile lesions, imaging techniques, or clinical symptoms. This diagnosis is confirmed by a histopathological examination of a core biopsy of the primary lesion. However, a biopsy is very invasive, quite difficult to obtain and causes great discomfort to the patient. Because tissue (re) biopsy is often a problem, the use of liquid biopsies has become extremely popular in recent years. While the detection of diagnostic, prognostic and predictive biomarkers is generally performed on tissue samples, detection on liquid biopsies shows promise. Currently, liquid biopsy analysis is mainly focused on plasma testing. Compared to tissue tests, blood tests are minimally invasive. While a blood sample is considered minimally invasive, a skilled caregiver is required to draw blood from patients. In addition, the patient's health status may not allow for additional blood draws. Obtaining urine, on the other hand, is non-invasive, does not depend on the health status of the patient, is without limitation on volume or frequency of collection, and can be performed at home or at the physician's office. There is a huge variety of biomarkers in liquid biopsies, including circulating tumor cells (CTCs), cell free nucleic acids (cfNA), exosomes and proteins that show promise for non-invasive testing. Depending on the type of molecule, different "omic" technologies (i.e. genomics, transcriptomics, proteomics and metabolomics) are used to detect them. Realizing the potential of urine as a liquid biopsy requires research into optimal collection methods and storage conditions for the detection of biomarkers. Colli-Pee® was developed by Novosanis and allows to collect urine in a standardized and volumetric way. If collection methods and storage conditions can be standardized, yellow can become the new red and urine can replace or equate blood in cancer detection.

Researcher(s)

Research team(s)

Funding

  • VL. INST.

Project type(s)

  • Research Project