Identifying novel therapeutic targets in esophageal, gastric and hepatocellular carcinomas using advanced close-to patient models
Among the gastrointestinal cancers, advanced esophageal and gastric cancers (EGC), and hepatocellular carcinomas (HCC) are major causes of mortality. The overall 5-year survival rate for esophageal and gastric carcinoma is approximately 25% and for HCC 50%, as the majority of patients is diagnosed when they already have advanced disease. This group of patients has a median survival of less than one year, despite several extensive chemo- and chemoradiotherapy in case of EGC and poor responses to limited treatment options in case of HCC. Novel therapeutic interventions are urgently needed in these cancers. To identify and test novel targets for therapeutic interventions advanced, close to patients models are required. Therefore we will set-up a PDXO screening platform composed of patient-derived mouse Xenograft (PDX) models and patient derived organoids (PDO) for EGC and HCC and use them to identify and test novel therapeutic targets. Based on pilot studies we will first investigate endoglin as a potential target. Endoglin is a co-receptor for members of the transforming growth factor-β family and originally identified on angiogenic endothelial cells with a crucial role in developmental- and tumor angiogenesis. More recently endoglin expression has also been detected on epithelial tumor cells and on cancer-associated fibroblasts (CAFs), where it plays an important role in driving tumor growth and metastases, via interaction with epithelial tumor cells (Paauwe et al CCR 2018). In this project we want to not only further investigate the role of endoglin in the progression of EGC and HCC, but also its potential as a therapeutic target. This study aims to set up a PDXO platform, reveal the potency of this platform to identify and test novel therapeutic targets and reveal novel roles for endoglin in the progression of EGC and HCC.
Sarah Hakuno graduated from Biomedical Sciences (University of Leiden) in 2019 and then started her PhD at the department of Gastroenterology and Hepatology under the supervision of Prof.Dr.Ir. Hein Verspaget, Dr. Luuk Hawinkels and Dr. Marije Slingerland.
Leids Universitair Medisch Centrum
2333 ZA Leiden
2300 RC Leiden