Rossella Reddavid1, Simona Corso2, Hogla Aridai Resendiz Aguilar1, Sara Ruscio1, Silvia Sofia1, Daniel Moya-Rull2, Stefania Durando3, Silvia Giordano2 and Maurizio Degiuli1*
1Department of Oncology, University of Turin, Italy
2Department of Oncology, University of Torino, Italy
3Department of Oncology, Candiolo Cancer Institute, Italy
Background: 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. Methodology: 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. Results: We identified 10 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 sub serosal layer. Tumour engraftment rate ranged from 0 to 100%, despite the technique. Metastases were observed in 40% of PDOX models implanted into the sub serosal 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. Conclusion: 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 sub serosal 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.
Gastric cancer; Stomach tumour; PDOX; Orthotopic transplantation; PDX; Model validity tool
Reddavid R, Corso S, Aridai Resendiz Aguilar H, Ruscio S, Sofia S, Moya-Rull D, et al. Patient-Derived Orthotopic Xenograft Model in Gastric Cancer: A Systematic Review. Clin Surg. 2019; 4: 2606..