Pancreatic cancer (PC) is an extremely aggressive malignancy with one of the worst prognoses of all cancers with a median survival of less than one-year and an overall 5-year survival of <7%. With marked resistance to chemo- and radiotherapies, surgery is the only curative option. In patients with localized disease and no lymph node or extra-pancreatic metastases, complete surgical resection provides a five-year survival rate of 30-75%. However, >80% of patients diagnosed have unresectable primary tumor. The major cause for the late presentation is lack of early diagnostic biomarker(s). However, the low levels of circulating markers during the early stages drastically dampens the efficacy of many promising markers. A rapid, widely distributable technology with highly sensitive and specific diagnostic ability to discriminate real disease (resectable neoplasms) from confounding high risk groups including pancreatitis, benign pathologies (acute biliary obstruction, common bile duct stone, cholecithiasis) and non-malignant benign cystic neoplasms (serous pancreatic cystic neoplasms) could change the fate of PC patient. Serum-based assays are the most widely used tests for the detection of tumor markers in clinical settings. The ability to detect low levels of specific cancer biomarkers in human serum provides an effective test for early diagnosis. It has been demonstrated that mucins, specifically MUC4, are overexpressed in pancreatic cancer. MUC4 has proven to be more informative PC biomarker than current gold standard - CA19.9. However, most of the currently used diagnostic test methodologies lack the sensitivity to detect MUC4 in human serum. As a consequence there exists a critical need to develop sensitive and effective platforms for detecting MUC4. It has been demonstrated that a platform based on SERS readout strategy surpasses the analytical capabilities of conventional immunoassays including both ELISA and RIA to detect mucins in human serum. Furthermore, we have recently showed that SERS-based nano-immunoassay is capable of differentiating samples of control cases from those of pancreatic cancer patients. We propose to test the feasibility of implementation of the Surface-Enhanced Raman Scattering (SERS)-based immunoassay detection platform into a robust portable point-of-care methodology to be used for ultrasensitive, quantitative and rapid detection of cancer biomarkers. The proposed research in phase I will focus on (Aim 1) improving sample preparation procedure by incorporating a microfluidic ?lab-on-a-chip? module and automation protocols; that will reduce the labor burden and decrease sample size, thus increasing the potential of the platform for high-throughput sample screening. The clinical utility of the assay will be validated (Aim 2) by comparing the assay with the PC prognostic marker CA19.9 and clinically testing the SERS-based assay in high risk controls and pancreatic cancer patients samples. Once optimized and validated, the SERS-based immunoassay platform will be incorporated into a portable point-of- care (POC) device which would be the subject of the immediate Phase II submission.

Public Health Relevance

Pancreatic Cancer (PC) is lethal malignancy lacking early diagnostic markers. The presented project aims to develop a Surface Enhanced Raman Spectroscopy based technology for the sensitive detection of circulating MUC4, a highly potential marker. It will lead towards the development of a highly specific, sensitive tool for early detection of malignancy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
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Special Emphasis Panel (ZRG1-OTC-H (14)B)
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Rahbar, Amir M
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Sanguine Diagnostics and Therapeutics
United States
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Carmicheal, Joseph; Kaur, Sukhwinder; Batra, Surinder K et al. (2018) Hunting for transcription factors: STAT3 decoy in non-small cell lung cancer. Transl Lung Cancer Res 7:S254-S257
Jahan, Rahat; Macha, Muzafar A; Rachagani, Satyanarayana et al. (2018) Axed MUC4 (MUC4/X) aggravates pancreatic malignant phenotype by activating integrin-?1/FAK/ERK pathway. Biochim Biophys Acta Mol Basis Dis 1864:2538-2549
Smolsky, Joseph; Kaur, Sukhwinder; Hayashi, Chihiro et al. (2017) Surface-Enhanced Raman Scattering-Based Immunoassay Technologies for Detection of Disease Biomarkers. Biosensors (Basel) 7: