Patient-Derived Xenograft Models: An Emerging Platform for Translational Cancer Research

Abstract

Recently, there has been an increasing interest in the development and characterization of patient-derived tumor xenograft (PDX) models for cancer research. PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor and remain stable across passages. These models have been shown to be predictive of clinical outcomes and are being used for preclinical drug evaluation, biomarker identification, biologic studies, and personalized medicine strategies. This article summarizes the current state of the art in this field, including methodologic issues, available collections, practical applications, challenges and shortcomings, and future directions, and introduces a European consortium of PDX models.Significance: PDX models are increasingly used in translational cancer research. These models are useful for drug screening, biomarker development, and the preclinical evaluation of personalized medicine strategies. This review provides a timely overview of the key characteristics of PDX models and a detailed discussion of future directions in the field. Cancer Discov; 4(9); 998-1013.

Nanoparticle engineered TRAIL-overexpressing adipose-derived stem cells target and eradicate glioblastoma via intracranial delivery

“…S5). Unlike immortalized cell lines, these patient-derived GBM cells can better preserve tumor phenotype and predict clinically relevant outcomes (26). Our data showed that patientderived GBM cells formed microsatellites surrounding main tumor in vivo (Fig.…”

“…Third, membrane-bound TRAIL was chosen as a therapeutic agent overexpressed by polymeric nanoparticles, which markedly augment receptor clustering and apoptosis stimulation in cancer cells (30,31). Last, patient-derived GBM xenograft cells were used rather than immortalized cell lines, which have been shown to better at preserving tumor phenotype and predicting clinically relevant outcomes (26).…”

Patient-Derived-Tumor-Xenograft: modeling cancer for basic and translational cancer research

“…A plethora of evidence, including high fidelity in mutational status, transcriptome, histology, polymorphism and copy number variation, also supports the notion that PDTX models remarkably resemble the pathophysiology of human tumors more closely than traditional Cancer-derived xenograft (CDX) models [16]. This convincing data suggests PDTX are informative models to study clonal evolution along serial passages, at the rates reported in primary tumors [17][18][19][20][21][22][23][24]. Notably, PDTX grow within a rich host environment and the relationship between human tumors and mouse host elements have been proven to be critical for the successful engraftment, growth and response to therapy [25].…”

Targeting G-Quadruplex DNA Structures by EMICORON Has a Strong Antitumor Efficacy against Advanced Models of Human Colon Cancer

“…On the contrary, cell lines, even when propagated in vivo, are derived from cancer cells that have adapted to growth outside a natural tumor microenvironment, resulting in genetic changes that are distinct from the genetic stress imposed on tumors in patients (44). Notwithstanding some limitations due to the drift of stromal components from human to mouse, PDXs represent a great challenge for oncology drug development, if viewed as complementary to other preclinical models (45). In this study, we have demonstrated that PDXs showed fidelity to the original tumor, as they maintain the morphologic features of a poorly differentiated colon adenocarcinoma and conserved the same KRAS mutation in the region of exon 2 of codon 12, observed in tumor of patient.…”