The goal of this SBIR project is to develop a minimally intrusive, highly-sensitive risk-stratification tool to determine the need for invasive pancreatic cancer (PC) screening. PC is the 4th leading cause of cancer deaths in the US. While early stage disease is generally curable, the vast majority of patients are diagnosed in advanced, unresectable stages due in large part to the lack of a suitable candidate screening technology. Unfortunately, all current screening modalities (ERCP or EUS) suffer from a very high false positive rate, high cost, invasiveness, and risk of serious complications. This underlines the urgent need for developing an effective test that targets PCat an early stage. The present project is based on a novel biophotonics technology that is exclusively licensed to NanoCytomics by Northwestern Univ., Partial Wave Spectroscopic (PWS) microscopy ('nanocytology'), that has been shown to sense and quantify nanoscale early-stage tumorigenic alterations within histologically normal- appearing cells. PWS uses the phenomenon of field carcinogenesis, the concept that the genetic/epigenetic alterations that lead to PC are also reflected in endoscopically normal periampullary duodenal mucosa either through shared risk factors or secreted factors (cytokines etc) from the pancreatic juice. Although the duodenal cells in PC patients appear endoscopically and microscopically normal, there are profound epigenetic alterations (e.g. methylation, microRNA etc.) whose nanoscale corollary (e.g., high-order chromatin) are detectable by partial PWS. The detection of nanoscale structural alterations of the fertile tumorigenic field may allow to risk-stratify patients with early-stage cancers or precancerous lesions located anywhere in duodenum. Thus, our preliminary data showed that the PWS-detectable nano-morphological alterations of periampullary duodenal cells are a highly sensitive and specific biomarker for PC. To perform the academic to commercial transition and establish duodenal nanocytology as a commercially-viable, minimally-intrusive, and highly-sensitive pre-screen for PC, several steps must be completed. In the present Phase I SBIR project, standard operating procedures (SOP) that are optimized for stability, reliability and diagnostic potential will be developed and validated. The future steps of this project will include refinement and optimization of the PWS markers in Phase II (thus enhancing its diagnostic power), followed by a multi-center clinical trial critical for the eventual regulatory approval. We envision that PWS analysis of cells brushed from the periampullary duodenal mucosa of high-risk patients (new onset diabetics, family history, chronic pancreatitis, etc.) as well as those undergoing EGD for other indications will serve as a gauge of risk/probability and can be used to risk stratify and hence tailor screening/surveillance decisions thus identifying the subset of patients who may benefit from further screening (such as a pancreatic CT/MRI or EUS/ERCP). In the long term, duodenal PWS can be combined with the existing upper GI screening by ultrathin EGD, thus allowing for a pan-upper GI cancer screening.
Pancreatic cancer is the 4th leading cause of cancer deaths in the US with no effective screening procedures available. This SBIR project proposes a minimally intrusive and highly sensitive screening tool for patients who are at a higher risk for pancreatic cancer. This involves sampling of the duodenal mucosa during ultrathin esophago-gastroduodenoscopy, thus avoiding the complications and costs of the currently used techniques.