Mouse Models of Peritoneal Carcinomatosis to Develop Clinical Applications.

Ángela Bella,Leire Arrizabalaga,Pedro Berraondo,Myriam Fernández-Sendin,Fernando Aranda,Álvaro Teijeira,Claudia Augusta Di Trani,José Medina-Echeverz,Ignacio Melero,Assunta Cirella

doi:10.3390/cancers13050963

Abstract

Simple SummaryPeritoneal carcinomatosis mouse models as a platform to test, improve and/or predict the appropriate therapeutic interventions in patients are crucial to providing medical advances. Here, we overview reported mouse models to explore peritoneal carcinomatosis in translational biomedical research.Peritoneal carcinomatosis of primary tumors originating in gastrointestinal (e.g., colorectal cancer, gastric cancer) or gynecologic (e.g., ovarian cancer) malignancies is a widespread type of tumor dissemination in the peritoneal cavity for which few therapeutic options are available. Therefore, reliable preclinical models are crucial for research and development of efficacious treatments for this condition. To date, a number of animal models have attempted to reproduce as accurately as possible the complexity of the tumor microenvironment of human peritoneal carcinomatosis. These include: Syngeneic tumor cell lines, human xenografts, patient-derived xenografts, genetically induced tumors, and 3D scaffold biomimetics. Each experimental model has its own strengths and limitations, all of which can influence the subsequent translational results concerning anticancer and immunomodulatory drugs under exploration. This review highlights the current status of peritoneal carcinomatosis mouse models for preclinical development of anticancer drugs or immunotherapeutic agents.

Highlights

Peritoneal Carcinomatosis (PCa) refers to the metastatic involvement of the peritoneum, characteristic of advanced-stage cancer [1]
Treatments are only feasible in a small number of patients, and severe side-effects have been reported after peritoneal chemotherapy for PCa [5,6,7]
PCa xenograft models are based on the transplantation of human cancer cells or tissue into the peritoneal cavity of immunodeficient mice, such as athymic nude, non-obese diabetic (NOD), severe combined immunodeficiency (SCID), or NOD SCID gamma mice (NSG)

Summary

Introduction

Peritoneal Carcinomatosis (PCa) refers to the metastatic involvement of the peritoneum, characteristic of advanced-stage cancer [1]. While syngeneic orthotopic models mimic more efficiently the disease biology of human disease, their main drawback relates to the monitoring of tumor progression, which requires the use of reporter genes, invasive surgical procedures or imaging methods such as real-time in-life fluorescence and bioluminescence imaging. Despite these limitations, syngeneic mouse models offer clues and proofs of concept in immunocompetent hosts and thereby represent an excellent preclinical platform to test compounds based on immuno-oncology targets to treat cancer [11]. We provide a brief overview of reported mouse models to explore PCa in translational biomedical research (Figure 1)

PCa Syngeneic Models

PCa Human Xenograft and PDX Models

PCa Genetically Induced Models

Concluding Remarks