Patient-Derived Orthotopic Xenograft models in gastric cancer: a systematic review

Abstract

Patient-Derived Xenografts (PDXs) are, so far, the best preclinical model to validate targets and predictors of response to therapy. While subcutaneous implantation very rarely allows metastatic dissemination, orthotopic implantation (Patient-Derived Orthotopic Xenograft-PDOX) increases metastatic capability. Using a modified tool to analyze model validity, we performed a systematic review of Embase, PubMed, and Web of Science up to December 2018 to identify all original publications describing gastric cancer (GC) PDOXs. We identified ten studies of PDOX model validation from January 1981 to December 2018 that fulfilled the inclusion and exclusion criteria. Most models (70%) were derived from human GC cell lines rather than tissue fragments. In 90% of studies, the implantation was performed in the subserosal layer. Tumour engraftment rate ranged from 0 to 100%, despite the technique. Metastases were observed in 40% of PDOX models implanted into the subserosal layer, employing either cell suspension or cell line-derived tumour fragments. According to our modified model validity tool, half of the studies were defined as unclear because one or more validation criteria were not reported. Available GC PDOX models are not adequate according to our model validity tool. There is no demonstration that the submucosal site is more effective than the subserosal layer, and that tissue fragments are better than cell suspensions for successful engraftment and metastatic spread. Further studies should strictly employ model validity tools and large samples with orthotopic implant sites mirroring as much as possible the donor tumour characteristics.

Keywords: Gastric cancer; Model validity tool; Orthotopic transplantation; PDOX; PDX; Stomach tumour.