Novel diagnostic methods and treatment for Barrett’s Esophagus

Esophageal cancer (EAC) remains one of the leading causes of death in the general population. Barrett’s Esophagus (BE) is the leading risk factor of EAC. However, further investigation concerning the biology and pathogenesis of BE still needs further investigation. In this thesis, we aimed to address two main gaps in BE research: 1) studies on specific, minimally invasive, and cost-effective biomarkers to be accurately used to screen BE patients in the general population and; 2) studies to investigate the inhibition of BMP4 or BMP2/4 as potential molecular strategies to eradicate BE and consequently to prevent the highly malignant EAC. The first part of this thesis we explored the possibility of using different BMPs as a diagnostic strategy to discriminate BE patients in the overall population. Analysis of the plasma levels of BMP2, BMP4, and BMP5, in samples from BE patients and healthy subjects showed BMP5 as significantly associated with an increased risk of having BE. In the second part of this thesis, we report on investigations into the potential of the anti-BMP4 and anti-BMP2/4 llama-derived antibodies by defining their specificity and effectivity and further translational analysis of the anti-BMP llama-derived antibodies in the different in vivo mouse models. Anti-BMP2/4 llama-derived antibodies showed to be highly specific and selective inhibitors in vitro and in vivo, without side effects. The in vivo models described here helped emphasize BMP2 and BMP4 as crucial molecular therapeutic targets for treating BE.