Patient-Derived Xenograft Models of Pancreatic Cancer: Overview and Comparison with Other Types of Models

Abstract

Pancreatic cancer (PC) is anticipated to be second only to lung cancer as the leading cause of cancer-related deaths in the United States by 2030. Surgery remains the only potentially curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC), the most common form of PC. Multiple recent preclinical studies focus on identifying effective treatments for PDAC, but the models available for these studies often fail to reproduce the heterogeneity of this tumor type. Data generated with such models are of unknown clinical relevance. Patient-derived xenograft (PDX) models offer several advantages over human cell line-based in vitro and in vivo models and models of non-human origin. PDX models retain genetic characteristics of the human tumor specimens from which they were derived, have intact stromal components, and are more predictive of patient response than traditional models. This review briefly describes the advantages and disadvantages of 2D cultures, organoids and genetically engineered mouse (GEM) models of PDAC, and focuses on the applications, characteristics, advantages, limitations, and the future potential of PDX models for improving the management of PDAC.

Molecular and Functional Analysis of Choline Transporters and Antitumor Effects of Choline Transporter-Like Protein 1 Inhibitors in Human Pancreatic Cancer Cells

“…Recently, generating patient-derived tumor xenografts (PDXs) has become easier. These PDXs retain the characteristics of patient-derived tumors, thus they are expected to be used for the pathological analysis of tumors, stem-cell and tumor-marker analysis, and drug development [41]. In the future, PDX models should be used to evaluate the antitumor effects of Amb4269951 and Amb4269675.…”

A nano-predator of pathological MDMX construct by clearable supramolecular gold(I)-thiol-peptide complexes achieves safe and potent anti-tumor activity

“…Hence, patient-derived xenograft (PDX) models where xenograft primary or metastatic tumors directly from the patient were introduced into severe combined immunodeficient mice became increasingly popular for therapeutic screening, biomarker discovery, and especially the preclinical evaluation of drugs in the last decade 43 . Moreover, it has been proven that subcutaneously inoculated PDX models of pancreatic carcinoma retain the histological and stromal features of the parental tumor 44 , 45 . Thus, to further investigate the therapeutic efficacy of Nano-MP@PSI, we comparatively examined its effect with Nano- D PMI@PSI on tumor growth, tumor weight, tumor cell apoptosis, and levels of MDMX, p53 as well as p21, using NOD/SCID mice bearing the first passage of a high-grade malignant PDX tumor of pancreatic cancer derived from a surgically resected residual tumor that harbored wild-type p53 and mutant KRAS, APC, and PI3KCA (Figure 7 A).…”

Expanding the Spectrum of Pancreatic Cancers Responsive to Vesicular Stomatitis Virus-Based Oncolytic Virotherapy: Challenges and Solutions

“…We will break down these models by the genetic background of the mouse, and how PDAC is established in the mouse. For more comprehensive reviews of in vivo PDAC model systems, we refer to these papers [ 84 , 85 ].…”

“…We will break down these models by the genetic background of the mouse, and how PDAC is established in the mouse. For more comprehensive reviews of in vivo PDAC model systems, we refer to these papers [84,85] [86]. These are useful models for studies not focused on antitumor immune responses, such as drug screenings as it is procedurally relatively simple and economical [87].…”