2. Academic Validation
  3. 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

  • Mol Oncol. 2024 Oct 5. doi: 10.1002/1878-0261.13741.
Nataša Stojanović Gužvić 1,  Florian Lüke 1 2 3,  Steffi Treitschke 1,  Andrea Coluccio 1,  Martin Hoffmann 1,  Giancarlo Feliciello 1,  Adithi Ravikumar Varadarajan 1,  Xin Lu 1,  Kathrin Weidele 1,  Catherine Botteron 1,  Silvia Materna-Reichelt 1,  Felix Keil 3 4,  Katja Evert 3 4,  Florian Weber 1 3 4,  Thomas Schamberger 5,  Michael Althammer 5,  Jirka Grosse 3 6,  Dirk Hellwig 3 6,  Christian Schulz 3 7,  Stephan Seitz 3 8,  Peter Ugocsai 3 8,  Anke Schlenska-Lange 9,  Roman Mayr 10,  Ulrich Kaiser 2 3,  Wolfgang Dietmaier 4,  Bernhard Polzer 1,  Jens Warfsmann 1,  Kamran Honarnejad 1,  Tobias Pukrop 1 2 3,  Daniel Heudobler 2 3,  Christoph A Klein 1 3 5,  Christian Werno 1
Affiliations

Affiliations

  • 1 Fraunhofer Institute for Toxicology and Experimental Medicine ITEM-R, Germany.
  • 2 Department of Internal Medicine III, University Hospital Regensburg, Germany.
  • 3 Bavarian Cancer Research Center (BZKF), Regensburg, Germany.
  • 4 Insitute for Pathology, University of Regensburg, Germany.
  • 5 Experimental Medicine and Therapy Research, University of Regensburg, Germany.
  • 6 Department of Nuclear Medicine, University Hospital Regensburg, Germany.
  • 7 Department of Internal Medicine II, University Hospital Regensburg, Germany.
  • 8 Department of Obstetrics and Gynecology, University Hospital Regensburg, Germany.
  • 9 Department of Oncology and Hematology, Hospital Barmherzige Brüder, Regensburg, Germany.
  • 10 Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Germany.
PMID: 39367702 DOI: 10.1002/1878-0261.13741
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.

Keywords

CTC; liquid biopsy; personalized tumor therapy; salivary gland cancer; tumoroid culture.

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