Sanguine Diagnostics And Therapeutics, Inc. — Department of Health and Human Services SBIR Phase I: 300

Description

Abstract The goal of this Fast track application is to develop a non invasive diagnostic test based on MUC and MUC mucins that can serve as an adjunct to cytological analysis of fine needle aspirates FNAs for accurate prediction of malignancy in patients with cystic pancreatic lesions Due to asymptomatic nature and lack of methods for early detection andgt of pancreatic cancer PC patients present with an unresectable primary tumor with distant metastasis at the time of diagnosis While the overall year survival rate of pancreatic cancer is dismal signi cantly better outcomes have been reported for smaller tumors detected at an earlier stage Slow development of PC in conjunction with the better curative response of patients with early disease underscore the need of early detection of pancreatic cancer Pancreatic cystic lesions earlier considered to be rare are increasingly being recognized due to increased number of individuals being subjected to diagnostic imaging however their exact prevalence is unknown These cystic pancreatic lesions have variable malignant potential while mucinous cystic neoplasms MCNs and intraductal pancreatic mucinous neoplasms IPMNs have a high probability of developing into malignant lesions serous cystic neoplasms SCNs are considered benign Despite the critical need accurate discrimination between high and low risk cystic lesions is challenging due to their symptomatic and radiographic similarities Although cytologic examination of endoscopic ultrasound EUS guided fine needle aspirates FNAs has emerged as an indispensable part of presurgical evaluation in practice of such analyses are inconclusive and unreliable in discriminating between serous and mucinous lesions Using anti MUC MAb G generated by our group several studies have established that cell surface mucin MUC is promising prognostic and diagnostic biomarker Further MUC and MUC exhibited specificity for malignancy in EUS FNAs containing atypical ductal epithelial cells The central hypothesis of this proposal Detection of MUC and or MUC in pancreatic tissues EUS FNAs is positively correlated with the presence of already existing pancreatic cancer or cystic lesions with malignant potential and thus MUC staining is a powerful tool for the accurate prediction of malignancy and pre surgical stratification of patients with cystic lesions of the pancreas Studies proposed for Phase I will result in the development of a prototype kit for MUC MUC IHC Aim and provide proof of concept in support of the aforementioned hypothesis Studies proposed in Phase II will validate the significance of MUC immunostaining in a blinded trial and determine how MUC expression correlates with the clinical outcome of the solid cystic pancreatic diseases Aim Further we propose to test the prototype kit in a clinical setting CLIA Lab to validate performance Aim Overall the proposal will lead to the development of a clinical test to stratify patients for surgical intervention or surveillance in the context of pancreatic cystic lesions and PC Project Narrative Endoscopic Ultrasound EUS based Fine Needle Aspirates FNAs represent a valuable pre surgical diagnostic material for confirming the presence or risk malignant lesions in the pancreas however their diagnostic utility is limited due to the poor sensitivity of cytological analysis particularly in cases exhibiting atypical epithelial cells Accurate diagnosis of malignant lesions of the pancreas can provide opportunity for intervention at a curable stage and reduce the risk of surgery associate morbidity in patients harboring benign lesions The proposed studies will validate if MUC and MUC staining in EUS FNAs can predict the risk of malignant lesions and help in appropriate patient selection for surgical resection