Molecular characterization and prediction to assess outcomes in Barrett's esophagus and esophageal cancer

This thesis summarizes our efforts to identify molecular biomarkers needed for biology-based strategies for Barrett’s (BE) surveillance and esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) treatment.
Patients with EAC have a poor prognosis. Patients with a complete response to neoadjuvant chemo(radio)therapy may benefit from a wait-and-see strategy. A subset of EAC patients with poor response might benefit from targeted therapies, immunotherapy or immediate resection of the tumor. We identified mRNA and immune signatures associated with therapy response in patients with EAC undergoing neoadjuvant therapy. Cancer subtyping will form the basis for the application of personalized treatments. We report on three different biological subgroups in EAC, which can be easily distinguished on routinely processed tissues.
Only a low percentage of patients with BE will progress to EAC. This challenges the effectiveness of surveillance programs. Even more, patient with dysplastic BE undergoing endoscopic therapy are at risk of developing recurrence and malignant progression. We report on gene-expression signatures associated with malignant progression in patients with NDBE, which can be detected long before malignant degeneration occurs. We also report on biomarkers that in future can be used for prediction of therapy response in patients with dysplastic BE undergoing endoscopic ablation therapy.
Hodgkin lymphoma (HL) survivors have an increased chance of developing ESCC, which implies underlying carcinogenic mechanisms related to HL therapy. We report on commonalities and differences in gene-expression in sporadic and ESCC with a history of HL but also of the normally appearing adjacent esophageal mucosa of both groups.
The results described in this thesis are derived from preclinical studies, of which several will need further validation followed by implementation in clinical practice. The final goal is to improve outcomes, quality of life and cost-effectiveness of the care of these challenging patient populations.