CTC-derived pancreatic cancer models serve as research tools and are suitable for precision medicine approaches
Pancreatic ductal adenocarcinoma (PDAC) poses significant clinical challenges, often presenting as unresectable with limited biopsy options. Here, we show that circulating tumor cells (CTCs) offer a promising alternative, serving as a "liquid biopsy" that enables the generation of in vitro 3D models and highly aggressive in vivo models for functional and molecular studies in advanced PDAC. Within the retrieved CTC pool (median 65 CTCs/5 mL), we identify a subset (median content 8.9%) of CXCR4<sup>+</sup> CTCs displaying heightened stemness and metabolic traits, reminiscent of circulating cancer stem cells. Through comprehensive analysis, we elucidate the importance of CTC-derived models for identifying potential targets and guiding treatment strategies. Screening of stemness-targeting compounds identified stearoyl-coenzyme A desaturase (SCD1) as a promising target for advanced PDAC. These results underscore the pivotal role of CTC-derived models in uncovering therapeutic avenues and ultimately advancing personalized care in PDAC.
Authors
- Da Fu (ORCID: https://orcid.org/0000-0002-0878-2575)
- Tobias Gustavsson (ORCID: https://orcid.org/0000-0001-9798-5632)
- Alexandra Aicher (ORCID: https://orcid.org/0000-0002-8920-9577)
- Yaru Zhao (ORCID: https://orcid.org/0000-0002-0645-5298)
- Elisabetta Fenocchio (ORCID: https://orcid.org/0000-0001-6679-0955)
- Chiara Reina (ORCID: https://orcid.org/0009-0008-7082-3949)
- Alfredo Mellano (ORCID: https://orcid.org/0000-0002-9090-5123)
- Felice Borghi (ORCID: https://orcid.org/0000-0002-2431-2020)
- Mette Ø. Agerbæk (ORCID: https://orcid.org/0000-0001-5865-2034)
- Vanesa Gregorc (ORCID: https://orcid.org/0000-0001-7168-9704)
- Berina Šabanović (ORCID: https://orcid.org/0000-0002-0883-3248)
- Christopher Heeschen (ORCID: https://orcid.org/0000-0002-1158-8554)
- Thor G. Theander (ORCID: https://orcid.org/0000-0002-3509-7514)
- Preeta Ananthanarayanan (ORCID: https://orcid.org/0000-0002-9900-0435)
- Chenlei Wen (ORCID: https://orcid.org/0000-0003-3458-5409)
- Jiajia Tang (ORCID: https://orcid.org/0000-0001-6036-6133)
- Ming-Hsin Yang (ORCID: https://orcid.org/0000-0001-9093-1009)
- Anna Sapino (ORCID: https://orcid.org/0000-0003-3542-9571)
- Ali Salanti (ORCID: https://orcid.org/0000-0003-2207-5575)
- Qi Wang (ORCID: https://orcid.org/0009-0009-0575-9693)
- Quan Zheng (ORCID: https://orcid.org/0000-0002-4512-9233)
- Thomas Mandel Clausen (ORCID: https://orcid.org/0000-0001-7543-9622)
- Clara Csilla Meny
- Ke Jiang (ORCID: https://orcid.org/0000-0001-8369-1211)
- Baiyong Shen (ORCID: https://orcid.org/0009-0004-7447-9541)
- Huimin Wang (ORCID: https://orcid.org/0000-0001-9041-3738)
Institutions
- Semmelweis University (HU)
- University of Copenhagen (DK)
- Tri-Service General Hospital (TW)
- Shanghai Jiao Tong University (CN)
- China Medical University (TW)
- Ruijin Hospital (CN)
- Shanghai Cancer Institute (CN)
- Candiolo Cancer Institute (IT)
- National Defense Medical Center (TW)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2024-08-19
- DOI
- https://doi.org/10.1016/j.xcrm.2024.101692
- Citations
- 22
- Primary Topic
- Pancreatic and Hepatic Oncology Research
- Type
- article
- Field-Weighted Citation Impact
- 6.22
Funders
- National Science Foundation
- National Natural Science Foundation of China
- Erciyes Üniversitesi
- Shanghai Municipal Education Commission
- China Scholarship Council
- Ministry of Science and Technology, Taiwan
- Associazione Italiana per la Ricerca sul Cancro
- Shanghai Municipal Population and Family Planning Commission
- Novo Nordisk Fonden
- Shanghai Rising-Star Program
- Rete Oncologica del Piemonte e della Valle d'Aosta
- Seventh Framework Programme
- National Natural Science Foundation of China-Yunnan Joint Fund
- Institute for Information Industry, Ministry of Science and Technology, Taiwan
- FP7 Space
- Eurostars