Translational Gastrointestinal Oncology
Translating disease biology into new diagnostic applications holds great promise for improving outcome for patients. We characterize gastrointestinal pre-malignant and malignant lesions at DNA, RNA, and protein level by tumor profiling using -omics techniques for biomarker development, to stratify patient groups and arrive at individually tailored therapies. Disease biology is studied using pre-clinical model systems such as organoid cultures. Clinical validation is performed by making use of large series of patient sample collections derived from multi-center clinical trials.
Molecular pathogenesis of colorectal cancer
Our understanding of the natural history of colorectal adenoma-to-cancer progression is still incomplete. Whole Genome Sequencing (WGS) captures an accurate, unbiased and complete view of genomic characteristics of a tumor. We make use of WGS tumor profiling data to gain insight in the prevalence of chromosomal rearrangement structural variants (SVs), a type of DNA alterations that has not been studied extensively so far. We identified genes that are frequently affected in colorectal cancer. Ongoing studies involve functional validation of candidate drivers of tumor progression using adenoma-derived organoids as a model system. The results of these studies provide novel insights in the molecular mechanisms underlying tumor development and yield novel biomarkers for colorectal cancer.
Patient stratification
Liquid biopsies (i.e. blood samples) contain minute amounts of tumor material, can be obtained longitudinally and are less burdensome than tissue biopsies. We investigate whether analysis of liquid biopsy circulating tumor DNA (ctDNA) can be applied as biomarkers to better determine who to treat, how to treat, and when to treat patients. Detection of ctDNA after surgery of stage II or III CRC patients is highly prognostic for disease recurrence and may therefore guide decisions who (not) to treat with adjuvant chemotherapy (ACT). For observational studies we collect and analyze blood samples longitudinally from stage II (MEDOCC study) and stage III (PROVENC3 study) CRC patients, making use of the infrastructure of the Prospective Dutch CRC cohort (PLCRC). Moreover, the MEDOCC-CrEATE ctDNA biomarker-driven interventional clinical trial is ongoing, which aims to examine the willingness of stage II colon cancer patients with detectable ctDNA after surgery to accept ACT and whether ACT reduces the risk of disease recurrence in these patients. In patients with metastatic CRC we investigate the clinical utility of ctDNA as a biomarker for treatment response monitoring (DOLPHIN study).