The dramatic increase in the number of patients being diagnosed with incidental pancreatic cysts through improved imaging represents a unique opportunity to detect and treat cystic precursor lesions before the onset of malignancy. However, pancreatic cysts also represent a major clinical challenge because current diagnostics do not adequately reflect the biology of cyst malignant transformation. Misregulated pericellular proteolysis is a hallmark of invasive cancer. Therefore, we are exploiting the activities of proteases in cyst fluid to develop an enzyme-based diagnostic test for the sensitive and specific identification of pre-malignant pancreatic lesions. Our goals are to develop a rapid and minimally invasive assay that improves patient stratification over current standard diagnostic markers and guides clinical decision-making to avoid unnecessary surgical intervention. The Alaunus Biosciences diagnostic pipeline takes advantage of a substrate profiling technology developed in the Craik Laboratory at UCSF referred to as Multiplex Substrate Profiling by Mass Spectrometry (MSP-MS). The MSP-MS assay uses a peptide library platform to monitor global protease substrate specificity and kinetic efficiency in complex biological samples in an unbiased manner. Through applying this substrate profiling approach to small volumes of cyst fluid (
Public Health Relevance Statement: Project Narrative Early diagnosis is the single most important tool to delay or avoid cancer-related mortality. Many people undergoing abdominal MRI or CT scans today are found to have cysts in their pancreas, which in some cases can evolve into pancreatic cancer; however, it is currently very difficult to predict which cysts are true precursor lesions and which will remain asymptomatic. We are developing a minimally invasive and highly sensitive diagnostic assay to identify cysts with a high likelihood of progressing into pancreatic cancer to facilitate early detection of malignancy as well as avoid unnecessary and costly surgeries for cases with benign cystic lesions.
Project Terms: Abdomen; Adult; Affect; base; Benchmarking; Benign; Biochemical; Biological; Biological Assay; Biological Sciences; Biology; Blinded; cancer invasiveness; Carcinoembryonic Antigen; Classification; Cleaved cell; Clinic; Clinical; clinical decision-making; Clinical Management; clinical practice; cohort; Complex; cost; Coupled; Cyst; Cyst Fluid; Cystic Lesion; Data; design; Detection; Development; Diagnosis; Diagnostic; diagnostic assay; diagnostic biomarker; Diagnostic tests; Disease; Early Diagnosis; Early identification; Enzymes; Excision; Fine needle aspiration biopsy; Fluorescence; Fluorescence Resonance Energy Transfer; Fluorogenic Substrate; Foundations; Future; Generations; Goals; Guidelines; high risk; Image; improved; Kinetics; Laboratories; Lead; Lesion; Libraries; Liquid substance; Magnetic Resonance Imaging; Malignant - descriptor; Malignant neoplasm of pancreas; Malignant Neoplasms; Mass Spectrum Analysis; minimally invasive; Monitor; Morbidity - disease rate; Morphology; mortality; Operative Surgical Procedures; Pancreas; Pancreatic Adenocarcinoma; Pancreatic Cyst; Pathologic; Patient risk; patient stratification; Patients; Peptide Hydrolases; Peptide Library; Peptides; Performance; Phase; Premalignant; prognostic; Prognostic Marker; Proteolysis; Proteomics; Risk; Sampling; Scanning; screening; Sensitivity and Specificity; Small Business Innovation Research Grant; Stratification; Substrate Specificity; Survival Rate; Technology; tool; Transcription Factor AP-1; Transcription Factor AP-2 Alpha; Ultrasonography; United States; Validation; X-Ray Computed Tomography
