ISET technology makes Circulating Tumor Cells accessible to target PDAC mutant genes detection in pancreatic cancer with an accuracy demonstrated by a targeted scNGS

Rarecells Inc., a leading Liquid Biopsy company is pleased to announce the development of an innovative and accurate targeted digital single-cell Next-Generation Sequencing (scNGS) for single-nucleotide variant (SNV) method to detect mutant genes of pancreatic ductal adenocarcinoma (PDAC) circulating tumor cells (CTC) enriched by the ISET® technology. 

A peer-reviewed article, published in the journal Cancer Letters (click to access article), describes a Johns Hopkins Medicine study that validated PDAC CTC detection by a targeted scNGS method of three driver mutant genes (KRAS/TP53/SMAD4) with ISET®-enriched CTC of PDAC patients. Blood samples from patients with late-stage and metastatic PDAC, showed CTCs with SNVs of KRAS/TP53/SMAD4 and the positive confirmation of immuno-fluorescent staining with Pan-CK/Vimentin/CD45. While patients with early-stage disease and patients with benign pancreatic cyst did not show mutated CTCs.

PDAC is a devastating disease with a 5-year survival rate of less than 10%. Surgical resection of the local disease provides the greatest chance of cure, yet, approximately 80% of resected patients die with the overwhelming pattern of recurrence being systemic.

Thus, understanding the mechanisms of the underlying nature of systemic disease after margin-free resections will guide the development of more effective therapeutic strategies.

Previous work with ISET® demonstrated that the presence of mesenchymal-like CTC phenotype expressing both epithelial and mesenchymal markers is correlated with cancer recurrence in patients with pancreatic cancer. In the present study, the ISET^® technology provides access to this rare CTC phenotype for highly sensitive and specific targeted detection of mutated PDAC CTC using an innovative WGA-free digital scNGS workflow. This new sequencing technology has promising potential for broad applications using any custom-designed panels with specific interests of genes in any malignancies.

Davide Brechot – Rarecells, Inc. – commented: “This article adds to the existing evidence that CTC harvested by the ISET® technology are suitable for multiple downstream analysis. The validation of this innovative and affordable targeted digital scNGS analysis of mutated PDAC CTC enriched with ISET® technology provides the scientific community with a reliable PDAC CTC detection workflow. Although larger cohort studies are needed, this is an opening to a personalized medicine approach in pancreatic cancer patients targeting on CTCs.”