Prof. dr. Marjolein van Egmond, professor in Oncology and Inflammation, PI at the Department of Molecular Cell Biology & Immunology and staff member at the Department of Surgery.
Novel molecules will be developed that can engage neutrophils and T cells at the tumor site. The mode of action of these molecules will be tested in vitro, in ex vivo human tumor fragments and in vivo. In collaboration with Dr. Joris Erdmann (Department of Surgery) and Prof.dr. Stan de Graaf (Tytgat Institute) we also aim to establish a novel human ex vivo liver metastases perfusion model to investigate efficacy of molecules in a relevant clinical setting. We expect that improved performance of immunotherapy will lead to better clinical outcome, and less futile treatments. Additionally, the development of a translational ex vivo human liver metastases model for drug testing may contribute to reduce the use of animals for preclinical studies.
Barrett's esophagus is the precursor to esophageal adenocarcinoma. Barrett’s patients are offered endoscopic surveillance to detect esophageal cancer at a curable stage. However, endoscopic surveillance is highly inefficient. Dysplasia and early cancer occurs in a very small subset of patients, we are not able to predict which Barrett’s patients will progress to cancer and endoscopic surveillance is not cost-effective and burdensome to patients. Therefore, we need a more effective, preferably non-endoscopic surveillance strategy.
Dr. Lucas Duits, Medical Specialist, Gastroenterology and hepatology
In recent years, a trans-oral capsule-sponge test called EndoSign (not requiring endoscopy) has been extensively evaluated for screening purposes (detecting Barrett’s esophagus in at risk individuals). This capsule-sponge test also has the potential to act as a surveillance tool for risk stratification of known Barrett’s esophagus patients, but has not yet been evaluated as such.
Our GTOSS project has two phases. First we will develop and validate a genomic and methylation based assay that can predict the risk of neoplastic progression in Barrett’s patients. We use previously obtained genomic and methylation data from two high quality case-control cohorts.
ubsequently we will create a prospective cohort of Barrett’s patients with and without dysplasia in whom we obtain endoscopic biopsies and capsule-sponge samples. This cohort will be utilized to cross-validate the findings from the first part of the project (genomic and methylation risk prediction assay) on different sampling techniques.
With this project we aim to pave the way towards non-endoscopic non-invasive personalized risk assessment in Barrett’s surveillance.
Dr. Maria Themeli, Assistant Professor at the department of Hematology
This awarded project aims to apply an innovative design of activation-inducible costimulatory receptors, recently developed in the group of dr Themeli, in combination with novel VHH binders that target B7-H3 on GBM. This novel strategy will provide a local, tumor-specific lytic capacity, overcoming heterogeneous antigen expression patterns and improving functional persistence of CAR-T cells. If successful, this project will generate not only a new treatment option for GBM but also for other solid tumors and will also generate critical knowledge for the improvement of CAR-T cell therapy for non-malignant neurological diseases.
Endometrial cancer incidence is rising and current diagnostics rely on invasive biopsy procedures. In 90%, postmenopausal bleeding is the first symptom of EC. Yet, after assessment by a gynaecologist, only ~9% of women with postmenopausal bleeding have an underlying malignancy, underscoring the need for an accurate and patient-friendly test.
Dr. Maaike Bleeker, Clinical pathologist specializing in gynecological pathology
Prof. dr. Renske Steenbergen, Professor of Experimental Pathology
Methylation testing in urine would offer a simple and non-invasive approach to detect endometrial cancer. To enable accurate endometrial cancer detection in urine in symptomatic women, methylation marker discovery in urine by the genome-wide mapping of differentially methylated regions is needed. Recently, a novel genome-wide enzymatic methylation sequencing technology has been developed, which is, in contrast to conventional bisulfite sequencing, applicable to low amounts of fragmented urinary DNA.
In this research project an unbiased discovery analysis of DNA methylation markers on urine samples will be performed with the aim to identify discriminatory markers for a methylation test that allows accurate detection of endometrial cancer in urine of symptomatic women. In collaboration with Self-screen, a successful spin-off company of VUmc, a prototype test will be designed.
Using innovative technologies on urine samples, urinary methylation markers will be defined that can identify women at increased risk of endometrial cancer. Patient-friendly urine testing can reduce costs and burden on healthcare systems.
This article was written by the researchers for Cancer Center Amsterdam.