Patient-derived xenograft models for personalized medicine in colorectal cancer

摘要

Establishing superior preclinical models is critical for translational cancer research owing to the high failure rates of novel therapeutics in clinical studies. Even though cell line-derived xenograft models are easy to create, they have numerous limitations since these models do not represent the distinctive features of each cancer patient adequately. To circumvent the discrepancies between xenograft models and tumors, patient-derived xenograft (PDX) models have been developed. These models are established through the engraftment of tissue from a patient's tumor into an immune-deficient mouse, which preserves cell-cell interactions and tumor microenvironment. Since PDXs precisely replicate intratumoral heterogeneity, a range of chemotherapeutic agents can be tested on individual tumors. Colorectal cancer represents a unique case to demonstrate clinical perspectives revealed by PDX models since they surmount limitations of conventional ex vivo models. Even though PDX models have been associated with drawbacks with respect to prediction of clinical outcomes, they are currently the model of choice for preclinical investigations in colorectal cancer. In the current review, we provide an overview of the methodology and applications of PDX for colorectal cancer and discuss critical issues for the advancement of these models for preclinical research.