Translational Assays for Inflammatory Biomarkers for the Risk Stratification of Pancreatic Cystic Lesions

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PROJECT SUMMARY Advances in clinical imaging technologies have increased the incidental detection rate of cystic pancreatic lesions. However, patients remain at risk due to the lack of a definitive diagnosis that accurately assesses if these cysts are pre-malignant. In the absence of robust diagnostic indicators, clinicians must balance patient safety due to a cystic lesion's rapid and aggressive progression to a malignant pancreatic tumor with the severe financial and physical morbidity and mortality associated with surgical interventions. Retrospective studies have found almost a quarter of surgical interventions to address a pancreatic cyst are unwarranted. A confounder is that retrospective studies have also revealed that when clinicians use a wait-and-see approach, up to a quarter of patients receive surgical resection too late. The dual-edged nature of this process highlights the need for better early-stage diagnostic tools. There remains an unmet clinical need for diagnostic information that can accurately stratify the risk associated with pre-cancerous, fluid-filled pancreatic lesions that are commonly the first sign of concern. Currently, clinicians can obtain fluid from incidentally detected pancreatic cysts for chemical analysis of disease- associated molecular markers. Pancreatic cyst fluid samples are most often highly viscous, making it difficult to aliquot, and can be very limited in volume depending on the size of cyst. Furthermore, available biomarker assays lack sensitivity, can have long turnaround times, and require high sample volumes. These traits limit the amount and quality of information from single pancreatic cyst fluid samples. Clinicians must rely on their unique experiences when choosing between appropriate analyses, which further confuses attempts at standardization of clinical care. Amplified Sciences has developed a robust assay platform to analyze low-volume (down to 1 µL) clinical pancreatic cyst fluid samples for protease activity to distinguish non-mucinous from mucinous pancreatic cyst populations. In this proposal, Amplified Sciences is expanding the platform to provide higher content diagnostic information about the malignant potential of the mucinous pancreatic cyst population. Amplified Sciences assay and detection platforms are adaptable to new biomarker targets. This proposal aims to create a multidimensional assay panel that accurately determines the risk of pancreatic cysts progression to cancer. A combination of three (3) markers under investigation by collaborators at Alaunus Biosciences and UCSF show promise to stratify the grade of dysplasia in a limited number of clinical mucinous pancreatic cyst samples. This proposal will 1) validate the capacity of these markers to distinguish low- from high-grade dysplasia in retrospective mucinous clinical samples and 2) translate low-volume assays for these markers into CLIA-ready protocols to enable stacking of assays on individual samples. Upon completion, a novel assay panel will be available that uses minimal cyst fluid volumes to quantitate the validated biomarkers, comprising a new method for clinicians to maximize accurate diagnostic information from precious clinical samples with rapid turnaround.