Improving accessibility to pancreatic cancer with circulating tumour cell technologies for targeted molecular therapeutics

Pancreatic adenocarcinoma is one of the most lethal malignancies with majority of patients having already developed metastases at presentation. Diagnosis is typically made by endoscopic ultrasound guided biopsy which remains a procedure where often samples are insufficient for diagnosis. Particularly in pancreas cancer where tissue access is limited, circulating tumour cells (CTC) is an attractive target for non-invasive therapeutic monitoring as they can reflect the evolving mutational profile of the disease. Unfortunately, the isolation of CTCs is technically challenging and to date only enumeration assays of limited clinical utility have been described in pancreatic cancer. The ex-vivo expansion of CTCs would greatly increase the amount of data that can be obtained from a single liquid biopsy. In this proof-of-concept study, we established CTC cultures from the peripheral blood of patients with pancreatic cancer at various stages of disease progression. CTC isolation and culture conditions were optimised, and tumour status was confirmed by identification of KRAS mutation with demonstration of tumourigenicity in mice. CTC lines were characterised with proteomics and compared against profiles of paired biopsy derived organoids and primary tumour samples where available. Our study has established CTC lines that provide the opportunity to personalize therapy in real-time by taking into account the temporal evolution of disease. Based on this proof-of-concept study, we have expanded the clinical utility of CTC cultures for drug sensitivity screening and therapeutic biomarker discovery.