Our group aims to advance precision treatment for gastrointestinal and hepatobiliary cancers. Our research is translational, operating in between bench and bedside. We aim to address clinically relevant questions of oncogene targeting in GI Cancers, employing molecular profiling techniques and patient-derived organoid modelling. Moreover, we develop and employ molecular monitoring technologies, aiming to personalize cancer treatment based on individual treatment responses.
Our laboratory focuses on
1. Therapeutic targeting of RAS and BRAF oncogenes in GI Cancers
2. Understanding and overcoming acquired resistance to targeted treatment
3. Organoid modelling of colorectal and pancreatic cancer
4. Molecular response monitoring and response-driven cancer treatment
1. Oncogene targeting in GI cancers
Therapeutic targeting of driver oncogenes has been a major success in clinical oncology. In the field of GI Cancers, recent advances in molecular profiling, together with the development of novel compopunds targeting BRAF and, more recently, KRAS oncogenes have opened up new possibilities of personalized treatment. Our research aims to advanced precision treatment in the clinic and, in parallel, model targeted treatment in the lab, employing patient-derived disease models.
2. Acquired resistance to targeted treatment
A major clinical limitation to the successful targeting of cancer oncogenes is the emergence of acquired resistance in patients. For instance, clinical responses to novel KRAS inhibitors or BRAF inhibitor combinations in GI cancers have proven rather short-lived, limited by rapidly emerging resistance, which is often polyclonal, A key objective of our research is to better understand the molecular mechanisms of acquired resistance in these tumors and to work out strategies how to delay, modify and overcome acquired resistance in GI cancers.
3. 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. In the lab, we have established protocols to derive PDOs from colorectal and pancreatic cancers with 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.
4. Molecular response monitoring
Another key focus of the lab is to 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 (tumor-informed panels). With these panels, we perform longitudinal analysis of patient plasma, and fnd ctDNA dynamics to be highly predictive of clinical outcome. Next steps are to prospectively employ these panel in interventional clinical trials.