The era of omics has ushered in the hope for personalized medicine. Proteomic and genomic strategies that allow unbiased identification of genes and proteins and their post-transcriptional and -translation modifications are an essential component to successful understanding of disease and the choice of imaging targets. However, the enormity of the genome and proteome and limitations in data analysis make it difficult to determine the targets that are particularly relevant to human disease and will be good targets for molecular imaging. Methods are therefore needed that allow rational identification of targets based on function, relevance to disease, and suitability for molecular imaging.
Screening methodologies such as phage display, SELEX, and small-molecule combinatorial chemistry have been widely used to discover specific ligands for cells or tissues of interest. Those ligands can be used in turn as affinity probes to identify their cognate molecular targets when they are not known in advance. In addition, those ligands can be developed into molecularly targeted drug delivery and imaging agents.
Through this lecture, we will explore one clinical scenario: pancreatic ductal adenocarcinoma (PDAC) as an application for target identification, imaging and therapeutic agent development. PDAC is among the most lethal of human cancers due to its marked resistance to existing chemo- and radiotherapies. Unlike a number of other solid tumors, which have robust methods for early detection, there have been no significant improvements in PDAC survival over the past 40 years despite a large number of clinical trials of both conventional and targeted therapies. Like other solid cancers, early detection that allows complete surgical resection offers the best hope for longer survival, unfortunately, most patients are diagnosed with metastatic disease due to the lack of specific symptoms and absence of suitable biomarkers for early detection.