An Annotated Biobank of Triple-Negative Breast Cancer Patient-Derived Xenografts Features Treatment-Naïve and Longitudinal Samples during Neoadjuvant Chemotherapy

Authors

Amanda L Rinkenbaugh
Yuan Qi
Shirong Cai
Jiansu Shao
Faiza Baameur Hancock
Sabrina L Jeter-Jones
Xiaomei Zhang
Emily Powell
Lei Huo
Rosanna Lau
Chunxiao Fu
Rebekah Gould
Petra den Hollander
Elizabeth E Ravenberg
Jason B White
Gaiane M Rauch
Banu Arun
Clinton Yam
Alastair M Thompson
Gloria V Echeverria
Stacy L Moulder
W Fraser Symmans
Jeffrey T Chang
Helen Piwnica-Worms

Language

English

Publication Date

11-3-2025

Journal

Cancer Research

DOI

10.1158/0008-5472.CAN-24-5023

PMID

40801311

PMCID

PMC12456255

PubMedCentral® Posted Date

9-24-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Triple-negative breast cancer (TNBC) that fails to respond to neoadjuvant chemotherapy (NACT) can be lethal. Developing effective strategies to eradicate chemoresistant disease requires experimental models that recapitulate the heterogeneity characteristic of TNBC. To that end, we established a biobank of 92 orthotopic patient-derived xenograft (PDX) models of TNBC from the tumors of 75 patients enrolled in the ARTEMIS clinical trial (NCT02276443), including 12 longitudinal sets generated from serial patient biopsies collected throughout NACT treatment and from metastatic disease. Models were established from both chemosensitive and chemoresistant tumors, and nearly 30% of the PDX models were capable of metastasizing to the lungs. Comprehensive molecular profiling demonstrated conservation of genomes and transcriptomes between patient and corresponding PDX tumors, with representation of all major transcriptional subtypes. Transcriptional changes observed in the longitudinal PDX models highlighted dysregulation in pathways associated with DNA integrity, extracellular matrix interactions, the ubiquitin-proteasome system, epigenetics, and inflammatory signaling. These alterations revealed a complex network of adaptations associated with chemoresistance. Overall, this PDX biobank provides a valuable tool for tackling the most pressing issues facing the clinical management of TNBC.

Keywords

Animals, Female, Humans, Mice, Biological Specimen Banks, Drug Resistance, Neoplasm, Neoadjuvant Therapy, Triple Negative Breast Neoplasms, Xenograft Model Antitumor Assays

Published Open-Access

yes

Recommended Citation

Rinkenbaugh, Amanda L; Qi, Yuan; Cai, Shirong; et al., "An Annotated Biobank of Triple-Negative Breast Cancer Patient-Derived Xenografts Features Treatment-Naïve and Longitudinal Samples during Neoadjuvant Chemotherapy" (2025). Faculty, Staff and Student Publications. 5292.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5292