Correlation between drug sensitivity profiles of circulating tumour cell-derived organoids and clinical treatment response in patients with pancreatic ductal adenocarcinoma

Yuan Hung Wu, Yi Ping Hung, Nai Chi Chiu, Rheun Chuan Lee, Chung Pin Li, Yee Chao, Yi Ming Shyr, Shin E. Wang, Shih Chin Chen, Sheng Hsuan Lin, Yi Hsuan Chen, Yu Mei Kang, Shih Ming Hsu, Sang Hue Yen, Jeng You Wu, Kuan Der Lee, Huey En Tseng, Jia Ruey Tsai, Jui Hsiang Tang, Jeng Fong ChiouThierry Burnouf, Yin Ju Chen, Peng Yuan Wang, Long Sheng Lu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)208-218
Number of pages11
JournalEuropean Journal of Cancer
Volume166
DOIs
StatePublished - May 2022

Keywords

  • Antitumour drug screening assays
  • Circulating tumour cells
  • Liquid biopsy
  • Medical oncology
  • Pancreatic ductal carcinoma
  • Personalised medicine

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