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Breast cancer patient-derived microtumors resemble tumor heterogeneity and enable protein-based stratification and functional validation of individualized drug treatment

Authors :
Nicole Anderle
Felix Schäfer-Ruoff
Annette Staebler
Nicolas Kersten
André Koch
Cansu Önder
Anna-Lena Keller
Simone Liebscher
Andreas Hartkopf
Markus Hahn
Markus Templin
Sara Y. Brucker
Katja Schenke-Layland
Christian Schmees
Source :
Journal of Experimental & Clinical Cancer Research, Vol 42, Iss 1, Pp 1-25 (2023)
Publication Year :
2023
Publisher :
BMC, 2023.

Abstract

Abstract Despite tremendous progress in deciphering breast cancer at the genomic level, the pronounced intra- and intertumoral heterogeneity remains a major obstacle to the advancement of novel and more effective treatment approaches. Frequent treatment failure and the development of treatment resistance highlight the need for patient-derived tumor models that reflect the individual tumors of breast cancer patients and allow a comprehensive analyses and parallel functional validation of individualized and therapeutically targetable vulnerabilities in protein signal transduction pathways. Here, we introduce the generation and application of breast cancer patient-derived 3D microtumors (BC-PDMs). Residual fresh tumor tissue specimens were collected from n = 102 patients diagnosed with breast cancer and subjected to BC-PDM isolation. BC-PDMs retained histopathological characteristics, and extracellular matrix (ECM) components together with key protein signaling pathway signatures of the corresponding primary tumor tissue. Accordingly, BC-PDMs reflect the inter- and intratumoral heterogeneity of breast cancer and its key signal transduction properties. DigiWest®-based protein expression profiling of identified treatment responder and non-responder BC-PDMs enabled the identification of potential resistance and sensitivity markers of individual drug treatments, including markers previously associated with treatment response and yet undescribed proteins. The combination of individualized drug testing with comprehensive protein profiling analyses of BC-PDMs may provide a valuable complement for personalized treatment stratification and response prediction for breast cancer.

Details

Language :
English
ISSN :
17569966
Volume :
42
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Experimental & Clinical Cancer Research
Publication Type :
Academic Journal
Accession number :
edsdoj.9f907d0fd89e4335a6c06b86d472f767
Document Type :
article
Full Text :
https://doi.org/10.1186/s13046-023-02782-2