Patient-derived xenograft models in hepatopancreatobiliary cancer

Abstract

Abstract Animal models are crucial tools for evaluating the biological progress of human cancers and for the preclinical investigation of anticancer drugs and cancer prevention. Various animals are widely used in hepatopancreatobiliary cancer research, and mouse models are the most popular. Generally, genetic tools, graft transplantation, and chemical and physical measures are adopted to generate sundry mouse models of hepatopancreatobiliary cancer. Graft transplantation is commonly used to study tumour progression. Over the past few decades, subcutaneous or orthotopic cell-derived tumour xenograft models (CDX models) have been developed to simulate distinct tumours in patients. However, two major limitations exist in CDX models. One model poorly simulates the microenvironment of tumours in humans, such as the vascular, lymphatic and immune environments. The other model loses genetic heterogeneity compared with the corresponding primary tumour. Increased efforts have focused on developing better models for hepatopancreatobiliary cancer research. Hepatopancreatobiliary cancer is considered a tumour with high molecular heterogeneity, making precision medicine challenging in cancer treatment. Developing a new animal model that can better mimic tumour tissue and more accurately predict the efficacy of anticancer treatments is urgent. For the past several years, the patient-derived xenograft model (PDX model) has emerged as a promising tool for translational research. It can retain the genetic and histological stability of their originating tumour at limited passages and shed light on precision cancer medicine. In this review, we summarize the methodology, advantages/disadvantages and applications of PDX models in hepatopancreatobiliary cancer research.

Keywords

• PDX model
• Hepatopancreatobiliary cancer
• Humanized