Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer characterized by late diagnosis and poor prognosis, highlighting a critical need for improved diagnostic and prognostic tools.

The urgent necessity for enhanced early-stage diagnostic methods is emphasized, as most patients present with advanced disease, which significantly worsens their prognosis.

Liquid biopsy techniques, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and proteomics, are being investigated to improve PDAC diagnosis, prognosis, and management.

Proteomics has shown superior accuracy in diagnosing PDAC, particularly for early-stage detection, especially when used alongside the CA19-9 marker.

Currently, CA19-9 is the only widely used biomarker for PDAC prognosis, but it has limitations in sensitivity and specificity.

KRAS mutations are present in about 95% of PDAC cases, with specific mutations like KRAS-G12D linked to aggressive cancer and poorer outcomes, while KRAS-G12V and KRAS-G12R are associated with better survival rates.

Senior author Dr. Rohit Chandwani advocates for revising clinical guidelines to recommend routine molecular testing for all pancreatic cancer patients, as current guidelines only apply to late-stage cases.

A systematic review of literature from 2019 to 2024 identified 49 studies on liquid biopsy biomarkers for PDAC, revealing that ctDNA shows potential for detecting mutant KRAS, though its effectiveness in early-stage disease is limited.

While CTCs offer high specificity, they have demonstrated low sensitivity for early-stage PDAC and inconsistent prognostic results.

A study analyzing data from 1,360 patients with pancreatic tumors found that 29% had early-stage cancer, while 71% presented with late-stage tumors.

The findings from this research suggest that treatment plans for pancreatic cancer patients should be personalized based on their specific KRAS mutations.

This research was conducted by institutions including Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center, and was funded by the National Cancer Institute and the National Institute of Biomedical Imaging and Bioengineering.