@article{5270febbae214c13ba8bc78002094637,
title = "Correlation between drug sensitivity profiles of circulating tumour cell-derived organoids and clinical treatment response in patients with pancreatic ductal adenocarcinoma",
abstract = "Introduction: Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive and has poor prognosis. There are few biomarkers to inform treatment decisions, and collecting tumour samples for testing is challenging. Methods: Circulating tumour cells (CTCs) from patients with PDAC liquid biopsies were expanded ex vivo to form CTC-derived organoid cultures, using a laboratory-developed biomimetic cell culture system. CTC-derived organoids were tested for sensitivity to a PDAC panel of nine drugs, with tests conducted in triplicate, and a weighted cytotoxicity score (CTS) was calculated from the results. Clinical response to treatment in patients was evaluated using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria at the time of blood sampling and 3 months later. The correlation between CTS and clinical response was then assessed. Results: A total of 41 liquid biopsies (87.8% from patients with Stage 4 disease) were collected from 31 patients. The CTC-derived organoid expansion was achieved in 3 weeks, with 87.8% culture efficiency. CTC-derived organoid cultures were positive for EpCAM staining and negative for CD45 staining in the surface marker analysis. All patients had received a median of two lines of treatment prior to enrolment and prospective utility analysis indicated significant correlation of CTS with clinical treatment response. Two representative case studies are also presented to illustrate the relevant clinical contexts. Conclusions: CTCs were expanded from patients with PDAC liquid biopsies with a high success rate. Drug sensitivity profiles from CTC-derived organoid cultures correlated meaningfully with treatment response. Further studies are warranted to validate the predictive potential for this approach.",
keywords = "Antitumour drug screening assays, Circulating tumour cells, Liquid biopsy, Medical oncology, Pancreatic ductal carcinoma, Personalised medicine",
author = "Wu, {Yuan Hung} and Hung, {Yi Ping} and Chiu, {Nai Chi} and Lee, {Rheun Chuan} and Li, {Chung Pin} and Yee Chao and Shyr, {Yi Ming} and Wang, {Shin E.} and Chen, {Shih Chin} and Lin, {Sheng Hsuan} and Chen, {Yi Hsuan} and Kang, {Yu Mei} and Hsu, {Shih Ming} and Yen, {Sang Hue} and Wu, {Jeng You} and Lee, {Kuan Der} and Tseng, {Huey En} and Tsai, {Jia Ruey} and Tang, {Jui Hsiang} and Chiou, {Jeng Fong} and Thierry Burnouf and Chen, {Yin Ju} and Wang, {Peng Yuan} and Lu, {Long Sheng}",
note = "Funding Information: This work was supported by the TMU Research Center of Cancer Translational Medicine from the Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan [grant numbers DP2-110-21121-03-C-06-01 , DP2-110-21121-03-C-06-02 , DP2-110-21121-03-C-06-03 , DP2-109-21121-03-C-06-01 , DP2-109-21121-03-C-06-02 , DP2-109-21121-03-C-06-03 ]; the Ministry of Science and Technology [grant numbers MOST-110-2320-B-038-056 , MOST-110-2314-B-038-138 , MOST-109-2314-B-038-122 , MOST-109-2314-B-038-141 , MOST-109-2635-B-038-001 , MOST-109-2314-B-038-072 , MOST 106-2320-B-038-03 ]; Taipei Medical University [grant number TMU105-AE1-B13 ]; and National Health Research Institutes [grant number NHRI-EX109- 10713EI ]. The funders had no role in the design of the study, collection, analysis, and interpretation of the data, or the writing and publication of this manuscript. Funding Information: This work was supported by the Taipei Medical University (TMU) Research Center of Cancer Translational Medicine from the Featured Areas Research Center Program within the Higher Education Sprout Project framework by the Ministry of Education in Taiwan. The authors thank our patients for agreeing to participate in this study. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = may,
doi = "10.1016/j.ejca.2022.01.030",
language = "English",
volume = "166",
pages = "208--218",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
}