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 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.
Authors
- Andrea Coluccio
- Daniel Heudobler (ORCID: https://orcid.org/0000-0002-8790-4584)
- Anke Schlenska‐Lange
- Wolfgang Dietmaier
- D. Hellwig (ORCID: https://orcid.org/0000-0002-3056-0143)
- Thomas Schamberger
- Jirka Grosse (ORCID: https://orcid.org/0000-0002-9130-0804)
- Christian Werno (ORCID: https://orcid.org/0009-0001-1647-4804)
- Adithi R. Varadarajan (ORCID: https://orcid.org/0000-0002-9581-8598)
- Florian Lüke (ORCID: https://orcid.org/0000-0001-5252-287X)
- Kathrin Weidele (ORCID: https://orcid.org/0009-0008-9313-5057)
- Silvia Materna‐Reichelt
- Jens Warfsmann (ORCID: https://orcid.org/0000-0001-5041-2925)
- Roman Mayr (ORCID: https://orcid.org/0000-0003-1796-3260)
- Felix Keil (ORCID: https://orcid.org/0000-0002-0651-5916)
- Florian Weber (ORCID: https://orcid.org/0000-0001-7480-8828)
- Bernhard Polzer (ORCID: https://orcid.org/0000-0002-3797-9975)
- Christoph A. Klein (ORCID: https://orcid.org/0000-0001-7128-1725)
- Kamran Honarnejad (ORCID: https://orcid.org/0000-0001-7122-0615)
- Ulrich Kaiser (ORCID: https://orcid.org/0000-0003-0321-5245)
- Catherine Botteron (ORCID: https://orcid.org/0000-0001-9525-1723)
- Tobias Pukrop (ORCID: https://orcid.org/0000-0001-8781-8187)
- Steffi Treitschke (ORCID: https://orcid.org/0009-0009-7716-2044)
- Michael Althammer
- Katja Evert (ORCID: https://orcid.org/0000-0003-0984-5563)
- Nataša Stojanović Gužvić
- Xin Lü (ORCID: https://orcid.org/0000-0002-6587-1152)
- Christian Schulz (ORCID: https://orcid.org/0000-0002-4861-4517)
- Martin Hoffmann (ORCID: https://orcid.org/0000-0001-9863-1772)
- Péter Ugocsai
- Giancarlo Feliciello
- Stephan Seitz
Institutions
- University Hospital Regensburg (DE)
- Fraunhofer Institute for Toxicology and Experimental Medicine (DE)
- Krankenhaus Barmherzige Brüder (DE)
- University of Regensburg (DE)
Publication Details
- Journal
- Molecular Oncology
- Published
- 2024-10-05
- DOI
- https://doi.org/10.1002/1878-0261.13741
- Citations
- 1
- Primary Topic
- Salivary Gland Tumors Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.57
Funders
- Deutsche Forschungsgemeinschaft
- Deutsche Krebshilfe