journal contribution
posted on 2025-11-03, 08:40 authored by 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 <p>Histological comparison of patient and PDX samples from longitudinal sets</p>
Funding
Cancer Prevention and Research Institute of Texas (CPRIT)
Conquer Cancer Foundation (CCF)
Cazalot Family
University of Texas MD Anderson Cancer Center (MD Anderson)
Still Water Foundation
Winterhof Foundation
National Cancer Institute (NCI)
United States Department of Health and Human Services
Find out more...Allison and Brian Grove Endowed Fellowship for Breast Medical Oncology
Susan Papizan Dolan Fellowship in Breast Oncology
History
ARTICLE 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 A Robust TNBC Evaluation fraMework to Improve Survival clinical trial (ARTEMIS, 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.
The development of a patient-derived xenograft biobank that comprehensively captures the genomic and transcriptional diversity of triple-negative breast cancer promises to be a robust resource to investigate and overcome chemoresistance and metastasis.
