Language

English

Publication Date

6-1-2022

Journal

Journal of Mammary Gland Biology and Neoplasia

DOI

10.1007/s10911-022-09520-y

PMID

35697909

PMCID

PMC9433358

PubMedCentral® Posted Date

6-13-2022

PubMedCentral® Full Text Version

Post-print

Abstract

Historically, human breast cancer has been modeled largely in vitro using long-established cell lines primarily in two-dimensional culture, but also in three-dimensional cultures of varying cellular and molecular complexities. A subset of cell line models has also been used in vivo as cell line-derived xenografts (CDX). While outstanding for conducting detailed molecular analysis of regulatory mechanisms that may function in vivo, results of drug response studies using long-established cell lines have largely failed to translate clinically. In an attempt to address this shortcoming, many laboratories have succeeded in developing clinically annotated patient-derived xenograft (PDX) models of human cancers, including breast, in a variety of host systems. While immunocompromised mice are the predominant host, the immunocompromised rat and pig, zebrafish, as well as the chicken egg chorioallantoic membrane (CAM) have also emerged as potential host platforms to help address perceived shortcomings of immunocompromised mice. With any modeling platform, the two main issues to be resolved are criteria for "credentialing" the models as valid models to represent human cancer, and utility with respect to the ability to generate clinically relevant translational research data. Such data are beginning to emerge, particularly with the activities of PDX consortia such as the NCI PDXNet Program, EuroPDX, and the International Breast Cancer Consortium, as well as a host of pharmaceutical companies and contract research organizations (CRO). This review focuses primarily on these important aspects of PDX-related research, with a focus on breast cancer.

Keywords

Animals, Breast Neoplasms, Cell Line, Disease Models, Animal, Female, Heterografts, Humans, Mice, Rats, Swine, Xenograft Model Antitumor Assays, Zebrafish

Comments

This article has been corrected. See J Mammary Gland Biol Neoplasia. 2022 Jul 26;27(2):231.

Published Open-Access

yes

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