Methods for modeling tumor growth in mice in experimental studies of human gastric cancer

Abstract

Gastric cancer (GC) is a group of malignant tumors originating from the gastric mucosa cells. The highest incidence of GC is recorded in Japan, China and Russia, and the lowest one in the USA and New Zealand. Extensive molecular genetic research of GC has revealed its heterogeneity associated with the genomic instability of the tumor and the complexity of its phenotype due to simultaneous changes in several oncogenes and suppressors. This was the basis for the creation of the GC classification by molecular subtypes. The creation of a realistic preclinical model is essential for translational GC studies. Cancer cell lines and xenografts derived from them are among the most common preclinical models. They are easy to generate, but they also have limitations, since these models cannot sufficiently reproduce the unique characteristics of each cancer patient. Patient-derived xenografts (PDX) are currently the best model for testing targets and predictors of response to therapy. PDX models are created by transplanting surgically resected human tumors into immunodeficient mice. These models maintain morphological similarity and replicate the molecular characteristics of parental tumors providing an indispensable tool for assessing anticancer drug response. Statistical data from preclinical studies with PDX models can significantly save the time and resources required for clinical trials. Transgenic and knockout mouse models are also widely used in scientific laboratories in order to study specific genetic pathways of oncogenesis and develop experimental therapy for GC. This review discusses the molecular classifications of GC and experimental murine models that reproduce cancer in situ and are a universal platform for preclinical research in experimental oncology.