Precision oncology in esophagogastric cancer From biomarker to personalized treatment

Despite the benefits achieved through multimodality treatment, the prognosis of esophageal and gastric remains dismal. Hence, improvement of current therapeutic strategies is imperative. In this thesis, we focus on intensification of non-targeted treatment, as well as precision oncology in esophagogastric cancer with the use of targeted therapies. The results in this thesis show a lack of feasibility of administrating adjuvant chemotherapy in patients with resectable esophageal adenocarcinoma in an unselected cohort, suggesting a role for treatment intensification in the neoadjuvant setting. Moreover, our findings enable optimization of HER2 directed therapy in patients with resectable esophageal adenocarcinoma by broadening our understanding of HER2 targeting through potential interactions with the tumor immune microenvironment, unraveling resistance mechanisms, and identifying predictive biomarkers which could be used for patient stratification. Furthermore, we investigated targeting of angiogenesis through the multikinase inhibitor regorafenib in advanced gastroesophageal cancer, providing biomarkers for patient selection and suggestions for novel treatment combinations. Taken together, these findings can guide the development of novel therapeutic strategies in patients with esophagogastric cancer, ultimately aiming to improve the overall outcome of patients with esophageal and gastric cancer.