Biomarkers in gastro-esophageal cancer From bedside to bench and back

The aim of this thesis was to identify and validate biomarkers in esophagogastric cancer (EC) to help guide clinical practice.
In the first part of the thesis, we investigated the currently used biomarker HER2, aiming to improve the treatment for HER2-positive EC patients. We found that applying a strict definition of HER2 status increases the likelihood of including positive discordant patients that might benefit of trastuzumab addition to a chemotherapy backbone. Next, we demonstrated that it is feasible to add HER2 targeted therapy (trastuzumab and pertuzumab) to neoadjuvant chemoradiation (nCRT) in HER2 positive patients with EC.
In the second part of the thesis, we aimed to identify additional biomarkers with clinical significance to predict prognosis, therapy resistance and to explore potential novel therapeutic strategies. We demonstrate that the tumor-immune microenvironment is a promising prognostic biomarker. Furthermore, we identify resistance mechanisms to nCRT in tumor tissue and blood and show novel therapeutic strategies to overcome these resistance mechanisms. Lastly, we investigated circulating tumor DNA (ctDNA) as a modality to prognosticate and monitor disease response.