The University of Texas MD Anderson Cancer Center

Principal Investigator (contact): Subrata Sen, PhD
Institution: The University of Texas MD Anderson Cancer Center

Principal Investigator: Ann Killary, PhD
Institution: The University of Texas MD Anderson Cancer Center

Synopsis of Research and Network Resources

Title of the PCDC Project

CIRCULATING BIOMARKERS AND IMAGING FOR EARLY DETECTION OF PANCREATIC CANCER

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer related deaths by organ site and is predicted to be the second leading cause of cancer deaths by the year 2030. Due to lack of clinically detectable symptoms, most cases are diagnosed late with locally advanced or metastatic disease. If PDAC is detected early (≤ stage IIB), surgical resection results in substantially improved survival compared to advanced disease (≥ stage III).  Identification of biomarkers for early detection of PDAC is an urgent need because currently there are no clinically validated biomarkers for this purpose. Detection of resectable PDAC or advanced precursor lesions (PanIN-3/high-grade PanIN) is essential for curative intervention.

Description of the Project

We have been developing circulating biomarkers implicated in cancer relevant pathways and precision imaging techniques for detection of resectable PDAC. Validated early stage biomarkers and additional pathway-based biomarkers upregulated in PanIN lesions will be screened for their ability to detect precursor disease. Due to low incidence of PDAC in the general population (age adjusted incidence in subjects >50 years age: 38/100,000), even biomarkers with 99% sensitivity and specificity would falsely identify 1000 subjects as having pancreatic cancer in a population of 100,000 subjects screened. Thus, we have proposed a three tiered approach for screening of early stage asymptomatic pancreatic cancer in the clinic. The first tier would entail identifying individuals at high risk of pancreatic cancer based on unique clinical phenotypes (New onset Diabetes: up to 8 fold risk; chronic pancreatitis: up to 3 fold risk; family history of disease: 2-13 fold risk etc.) and/or testing positive for biomarkers of early stage disease. The second tier would be non-invasive imaging. Those with abnormal imaging results would be recommended for the third tier screening involving invasive tests. We propose to validate early stage biomarker and novel imaging tools in longitudinal and high-risk cohorts to stratify the population for surveillance and, if needed, core biopsy of the lesions.    

Our specific aims are: 1) Validation of pathway-associated biomarker signatures of early stage resectable tumors and precision imaging utilizing early stage cohorts. 2) Validation of PDAC early precursor lesion associated biomarker signatures and precision imaging developed with genetically engineered mouse models harboring precursor lesions and well characterized large longitudinal patient cohorts. 3) Blinded validation of early detection biomarker signatures in retrospective pre-diagnostic samples. 4) Prospective screening of integrated biomarkers and imaging using risk scores in pre-diagnostic high risk PDAC cohorts and Pancreatic Cancer High Risk Clinic (PCHRC) patients.

Resources for Sharing (e.g., description of cohorts, technologies)

We are generating biorepositories with well-annotated human and mouse samples in conjunction with an imaging database. We collect a variety of biospecimens including blood and cystic fluid across a spectrum of patients, including those with pancreatic cancer, cystic lesions, and high-risk individuals.

Opportunities for Collaboration

We welcome opportunities to collaborate. Please contact the PIs at the provided e-mail addresses to discuss collaborations.