Experimental GI Oncology Lab

Keywords

Oncogenic signalling, GI oncology, organoid modelling, acquired resistance, ctDNA monitoring

Summary & Mission statement

Our research is translational, operating inbetween bench and bedside, addressing clinically relevant questions of oncogenic signalling in GI Cancers.  We aim to advance precision treatment for patients with gastrointestinal and hepatobiliary cancers.

Overview

1. Oncogene targeting in GI cancers and acquired resistance

We focus on targeted treatment of BRAF- and KRAS-mutated GI Cancers. We employ patient-derived disease models and model targeted treatment in vitro, aiming to improve oncogene targeting. A key objective of our research is to better understand the molecular mechanisms of acquired resistance and to work out strategies how to delay, modify and overcome acquired resistance in GI cancers.

2. Organoid modelling

Patient-derived tumor organoids (PDOs) are 3D tumor cultures growing in matrix. PDOs retain genotype and much of the phenotype of individual patient tumors. We have established protocols to derive PDOs from colorectal and pancreatic cancers at a very high success rate. We employ these cultures to study tumor biology, model treatment and explore treatment resistance. In parallel we employ established cell lines for drug and genetic screening.

3. Molecular response monitoring

We develop and employ molecular monitoring tools for cancer patients undergoing cancer treatment. We establish digital PCR multiplex panels for the analysis of cell-free, tumor-derived DNA based on an individual`s tumor molecular profile. We perform longitudinal analysis of patient plasma, and find ctDNA dynamics to be highly predictive of clinical outcome. Next steps are to prospectively employ these panel in interventional clinical trials