Circulating Tumor DNA as a Biomarker in Pancreatic Cancer: Clinical Applications and Challenges.

Pancreatic cancer represents the most lethal malignancy among all gastrointestinal tumors. Recent medical advances, such as targeted therapy and immunotherapy, increasingly rely on tumor molecular profiling to tailor treatment of patients with advanced cancer. Given the risks associated with invasive biopsy, circulating cell-free DNA (cfDNA) has emerged as a cutting-edge approach for the detection and monitoring of cancer. The minimally invasive operation, coupled with the sensitive and timely detection of cancer across multiple clinical application, makes cfDNA a potential solution to transform precision oncology. Despite the advances, the expected widespread application of liquid-biopsy is still limited due to a series of substantial challenges in technique and clinical settings. In this article, we discuss technologies and methodologies in the detection of cfDNA. The opportunities to address substantial challenges, including achieving clinical meaningful detection sensitivities, enhancing of assay accessibility, evaluating the clinical sensitivity of circulating tumor DNA (ctDNA) burden in clinical settings, are highlighted to support the integration of liquid biopsies into cancer treatment. The most recent ctDNA-associated studies are summarized to provide a whole picture of the application of ctDNA in the adaptive management and surveillance of pancreatic cancers.