Validation of a model of orthotopic transplantation of human gastric cancer in NOD SCID mice for generation of a gastro-esophageal patient-derived xenograft (PDX) platform to improve therapeutic outcome

Gastric cancer is the third leading cause of cancer mortality worldwide. Surgery is the only curative treatment strategy; conventional chemotherapy has shown limited efficacy and only two molecular therapies are currently approved (Trastuzumab for HER2+ GCs and Ramucirumab). To explore in depth the molecular mechanisms sustaining tumor growth and response to therapy, animal models are very useful. At the moment, the best preclinical model to validate targets and positive/negative response predictors of response to therapy is represented by Patient-Derived Xenografts (PDXs), an experimental model that retains the principal histologic and genetic characteristics of the donor tumor, is predictive of clinical outcome and is a valuable tool for personalized medicine decisions. Indeed, this strategy combines the flexibility of preclinical analysis with the informative value of population-based studies. We have recently generated a molecularly annotated colony of gastro-esophageal PDXs (at the moment >90 PDXs) by subcutaneous transplantation in NOD SCID mice. This platform also comprises primary cell lines and 3D-coltured organoids. Although this platform has already been helpful in investigating therapeutic approaches against activated receptor tyrosine kinases, the subcutaneous tumor implantation very rarely allows metastatic dissemination.