"Use of a mouse model to improve methods to diagnose pancreatic cancer in humans"
Pancreatic ductal adenocarcinoma (PDA) is one of the most deadly cancers with annual incidences nearly synonymous with mortality, largely because the majority of patients present with unresectable or frank metastases at the time of diagnosis. Methods that enable earlier detection and more accurate diagnoses to inform decisions in the clinic are therefore greatly needed, yet improvements are paradoxically hindered by the insidious nature of PDA. Thus, mouse models that faithfully recapitulate human PDA are of great use. I propose to use a mouse model of PDA in conjunction with a high-throughput antibody microarray to identify tumor-derived plasma biomarkers that could be used for both early detection and in aiding in informing diagnoses in the clinic. Relevant markers validated and isolated using available tumor tissue and serial collections of plasma in the mouse model will then be translated to studies involving interrogation of pre- and post-diagnostic human PDA plasma. Markers that translate from the mouse model to humans can then be assessed for their benefit as diagnostics or surrogates by reciprocally testing their relevance in conjunction with therapies in the mouse model. Collectively, this interdisciplinary project seeks to systematically distinguish biologically relevant biomarkers that could be of direct benefit in the clinic.