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  4. Cellular liquid biopsy provides unique chances for disease monitoring, preclinical model generation and therapy adjustment in rare salivary gland cancer patients
 
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2025
Journal Article
Title

Cellular liquid biopsy provides unique chances for disease monitoring, preclinical model generation and therapy adjustment in rare salivary gland cancer patients

Abstract
While cell‐free liquid biopsy (cfLB) approaches provide simple and inexpensive disease monitoring, cell‐based liquid biopsy (cLB) may enable additional molecular genetic assessment of systemic disease heterogeneity and preclinical model development. We investigated 71 blood samples of 62 patients with various advanced cancer types and subjected enriched circulating tumor cells (CTCs) to organoid culture conditions. CTC‐derived tumoroid models were characterized by DNA/RNA sequencing and immunohistochemistry, as well as functional drug testing. Results were linked to molecular features of primary tumors, metastases, and CTCs; CTC enumeration was linked to disease progression. Of 52 samples with positive CTC counts (≥1) from eight different cancer types, only CTCs from two salivary gland cancer (SGC) patients formed tumoroid cultures (P = 0.0005). Longitudinal CTC enumeration of one SGC patient closely reflected disease progression during treatment and revealed metastatic relapse earlier than clinical imaging. Multiomics analysis and functional in vitro drug testing identified potential resistance mechanisms and drug vulnerabilities. We conclude that cLB might add a functional dimension (to the genetic approaches) in the personalized management of rare, difficult‐to‐treat cancers such as SGC.
Author(s)
Stojanovic, Natasa  
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Lüke, Florian  
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Treitschke, Steffi  
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Keil, Felix
Hoffmann, Martin  
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Feliciello, Giancarlo  
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Varadarajan, Adithi Ravikumar
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Lu, Xin  
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Weidele, Kathrin  
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Botteron, Catherine
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Materna-Reichelt, Silvia
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Evert, Katja
Coluccio, Andrea
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Schamberger, Thomas
Althammer, Michael
Grosse, Jirka
Hellwig, Dirk
Schulz, Christian
Seitz, Stephan
Ugocsai, Peter
Schlenska‐Lange, Anke
Mayr, Roman
Weber, Florian
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Kaiser, Ulrich
Dietmaier, Wolfgang
Polzer, Bernhard Michael  
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Heudobler, Daniel
Warfsmann, Jens
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Pukrop, Tobias  
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Honarnejad, Kamran
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Klein Christoph A.  
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Journal
Molecular oncology  
Open Access
DOI
10.1002/1878-0261.13741
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English
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