Pancreatic Cancer CTCs Harvested by Leukapheresis Yield Organoids

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Organoids can be propagated from CTCs from patients with pancreatic cancer, potentially offering an approach to study treatment resistance.
Organoids can be propagated from CTCs from patients with pancreatic cancer, potentially offering an approach to study treatment resistance.

Circulating tumor cells (CTCs) collected during leukapheresis from patients with pancreatic ductal adenocarcinoma (PDAC) successfully propagated organoids, according to a study presented at the 2018 AACR Pancreatic Cancer: Advances in Science and Clinical Care conference in Boston, Massachusetts.1

Organoid modeling from needle biopsies of pancreatic tumors could predict clinical response to therapy, but this approach is invasive and technically challenging. Another approach is using CTCs, but this has been limited because CTCs generally produce a low yield of organoids. The aim of this study was to determine if CTCs harvested from leukapheresis would provide enough material to successfully propagate organoids.

The ongoing trial has enrolled 14 patients with PDAC to date, of whom, 10 underwent leukapheresis for 30 minutes. Leukapheresis yielded 1 x 103-5 CTCs. Organoids were successfully propagated from 7 of 10 patients within 1 week and for up to 3 months, regardless of stage of disease and prior treatment. The organoids were positive for EpCAM, cytokeratin, and KRAS codon 12 mutations.

The authors concluded that these data “suggest that establishment of organoid cultures can be accomplished from CTCs in a robust manner as long as a large number of cells are used to seed cultures.” Future studies are planned to evaluate treatment resistance and to potentially use this approach to guide treatment decisions.

Reference

  1. Rhim A, Lee AH, Manning SL, et al. Successful organoid establishment from circulating tumor cells: utilizing brief leukapheresis to collect large numbers of CTCs from patients with pancreatic cancer. Presented at: AACR Pancreatic Cancer: Advances in Science and Clinical Care; Boston, MA, September 21-24, 2018. Abstract A113.

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