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

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

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 wi...

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Main Authors: Nataša Stojanović Gužvić, Florian Lüke, Steffi Treitschke, Andrea Coluccio, Martin Hoffmann, Giancarlo Feliciello, Adithi Ravikumar Varadarajan, Xin Lu, Kathrin Weidele, Catherine Botteron, Silvia Materna–Reichelt, Felix Keil, Katja Evert, Florian Weber, Thomas Schamberger, Michael Althammer, Jirka Grosse, Dirk Hellwig, Christian Schulz, Stephan Seitz, Peter Ugocsai, Anke Schlenska‐Lange, Roman Mayr, Ulrich Kaiser, Wolfgang Dietmaier, Bernhard Polzer, Jens Warfsmann, Kamran Honarnejad, Tobias Pukrop, Daniel Heudobler, Christoph A. Klein, Christian Werno
Format: Article
Language:English
Published: Wiley 2025-07-01
Series:Molecular Oncology
Subjects:
CTC
liquid biopsy
personalized tumor therapy
salivary gland cancer
tumoroid culture
Online Access:https://doi.org/10.1002/1878-0261.13741
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Summary: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.
ISSN:1574-7891
1878-0261

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