Japan Digestive Disease Week 2025
Invited Lecture (JSGE)
October 30, 9:00–9:30, Room 1 (Kobe International Exhibition Hall No.2 Building Hall (North))
Invited Lecture-3
Liquid biopsy biomarkers for the early detection of pancreatic cancer
- Beckman Research Institute of the City of Hope
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal forms of cancer, largely due to its typically late diagnosis, limited effective treatment options, and the absence of robust early detection biomarkers. These factors contribute to the dismal 5-year survival rate of approximately 10% in PDAC patients. PDAC develops through a stepwise accumulation of genomic and epigenomic alterations, transforming normal pancreatic epithelium into invasive carcinoma, a process that can span 15 to 20 years from the first initiating mutational event. This lengthy latency presents a unique and critical window of opportunity for earlier disease detection and intervention, potentially leading to improved survival outcomes.
Efforts to capitalize on this window have driven the exploration of a broad range of molecular biomarkers for early detection, prognosis, and therapeutic prediction. While many biomarker candidates have emerged, non-invasive liquid biopsies, which allow molecular profiling from bodily fluids such as blood, urine, and stool, have received particular attention for early detection and post-surgical disease monitoring. In contrast, prognostic and predictive biomarkers - especially those informing therapeutic decisions - are still primarily reliant on analyses of surgically resected tissues, typically performed before the initiation of adjuvant chemotherapy. Key classes of analytes under investigation include: 1) Cell-free tumor DNA (ctDNA), which is used for detecting gene mutations and epigenetic DNA methylation patterns. 2) Cell-free RNAs, including mRNAs and small non-coding RNAs (ncRNAs): These have been shown to play central roles in the pathogenesis of PDAC.
Despite growing interest in these approaches, most are still in early developmental stages. While ctDNA-based assays offer high specificity, they often suffer from low sensitivity due to the limited quantities of tumor DNA present in circulation. Conversely, while cell-free RNA assays tend to be more robust, questions remain about their tissue specificity and biological origin. A promising avenue to address these limitations lies in the analysis of tumor-derived exosomes or extracellular vesicles (EVs) found in the bloodstream. These vesicles may provide a favorable balance of sensitivity and specificity, potentially overcoming key barriers to clinical implementation.
This presentation will provide an update on the current landscape of biomarker research in pancreatic ductal adenocarcinoma (PDAC), highlighting emerging opportunities as we advance toward a future of precision oncology in pancreatic cancer care.
Efforts to capitalize on this window have driven the exploration of a broad range of molecular biomarkers for early detection, prognosis, and therapeutic prediction. While many biomarker candidates have emerged, non-invasive liquid biopsies, which allow molecular profiling from bodily fluids such as blood, urine, and stool, have received particular attention for early detection and post-surgical disease monitoring. In contrast, prognostic and predictive biomarkers - especially those informing therapeutic decisions - are still primarily reliant on analyses of surgically resected tissues, typically performed before the initiation of adjuvant chemotherapy. Key classes of analytes under investigation include: 1) Cell-free tumor DNA (ctDNA), which is used for detecting gene mutations and epigenetic DNA methylation patterns. 2) Cell-free RNAs, including mRNAs and small non-coding RNAs (ncRNAs): These have been shown to play central roles in the pathogenesis of PDAC.
Despite growing interest in these approaches, most are still in early developmental stages. While ctDNA-based assays offer high specificity, they often suffer from low sensitivity due to the limited quantities of tumor DNA present in circulation. Conversely, while cell-free RNA assays tend to be more robust, questions remain about their tissue specificity and biological origin. A promising avenue to address these limitations lies in the analysis of tumor-derived exosomes or extracellular vesicles (EVs) found in the bloodstream. These vesicles may provide a favorable balance of sensitivity and specificity, potentially overcoming key barriers to clinical implementation.
This presentation will provide an update on the current landscape of biomarker research in pancreatic ductal adenocarcinoma (PDAC), highlighting emerging opportunities as we advance toward a future of precision oncology in pancreatic cancer care.