Prognostic and predictive biomarkers in pancreatic cancer: the role of circulating tumor cells and cell-free nucleic acids—a narrative review

Background and Objective: Pancreatic cancer (PCa) remains one of the most lethal malignancies, largely due to late-stage diagnosis, early metastatic spread, and limited responsiveness to conventional therapies. The absence of reliable biomarkers for early detection and treatment monitoring significantly hampers clinical management. This narrative review aims to summarize and integrate current evidence on the biological characteristics and clinical utility of circulating tumor cells (CTCs) and circulating free nucleic acids (cfNAs), including circulating tumor DNA (ctDNA) and circulating tumor RNA (ctRNA), in pancreatic cancer.

Methods: A narrative literature review was conducted using the PubMed, Scopus, and Web of Science databases. Articles published in English between 2000 and 2024 were screened using keywords related to pancreatic cancer, circulating tumor cells, circulating tumor DNA, circulating tumor RNA, and liquid biopsy. Relevant clinical and translational studies evaluating the prognostic, predictive, and diagnostic value of circulating biomarkers in pancreatic cancer were included.

Key Content and Findings: CTCs and cfNAs provide valuable insights into tumor biology, disease progression, and therapeutic response in pancreatic cancer. Numerous studies demonstrate that the presence and quantity of CTCs correlate with tumor differentiation, metastatic potential, and overall survival. ctDNA analysis, particularly KRAS and TP53 mutations, has shown promise in early detection, prognosis stratification, and monitoring treatment response in both early-stage and metastatic disease.

Conclusions: CTCs and circulating free nucleic acids represent promising biomarkers for improving the diagnosis, prognosis, and therapeutic monitoring of pancreatic cancer. Integrating multiple circulating biomarkers may enhance clinical decision-making and support personalized treatment strategies.