Data-Driven Prioritization and Review of Targets for Molecular-Based Theranostic Approaches in Pancreatic Cancer

Abstract

Molecularly targeted therapeutic and imaging strategies directed at aberrant signaling pathways in pancreatic tumor cells may improve the poor outcome of pancreatic ductal adenocarcinoma (PDA). Therefore, relevant molecular targets need to be identified. Methods: We collected publicly available expression profiles of patient-derived normal pancreatic tissue (n 5 77) and PDA samples (n 5 103). Functional genomic messenger RNA profiling was applied to predict target upregulation on the protein level. We prioritized these targets based on current status of preclinical therapeutic and imaging evaluation in PDA. Results: We identified 213 significantly upregulated proteins in PDA compared with normal pancreatic tissue. We prioritized mucin-1, mesothelin, g-glutamyltransferase 5, and cathepsin-E as the most interesting targets, because studies already demonstrated their potential for both therapeutic and imaging strategies in literature. Conclusion: This study can assist clinicians and drug developers in deciding which theranostic targets should be taken for further clinical evaluation in PDA.

Glypican 3 Overexpression across a Broad Spectrum of Tumor Types Discovered with Functional Genomic mRNA Profiling of a Large Cancer Database

“…31 This tool provides whole-body information regarding (heterogeneity in) protein expression in a noninvasive manner and increasingly is being implemented in drug development and patient care. 32 FGmRNA profiling can be used as a tool to select suitable targets for molecular imaging, as has been shown by Koller et al 33 for pancreatic ductal adenocarcinomas.…”

A guideline for clinicians performing clinical studies with fluorescence imaging

“…However, it is increasingly questioned whether this is representative of the complete tumour due to tumour heterogeneity and variations in target expression over time. Data-driven methods based on genomic alterations are studied to identify and prioritize relevant targets for clinical trials (20). In addition, many targets (e.g., cell membrane receptors) are present in a microscopically heterogeneous pattern.…”

Validation of Novel Molecular Imaging Targets Identified by Functional Genomic mRNA Profiling to Detect Dysplasia in Barrett’s Esophagus

“…Publicly available microarray expression profiles of patient-derived primary EAC and NDBE samples generated with the Affymetrix HG-U133 plus 2.0 and the HG-U133A platforms were obtained from the Gene Expression Omnibus database [21]. Pre-processing, normalization, and quality control were performed as previously described [22]. Subsequently, FGmRNA profiling was applied to filter out non-genetic factors and extract the downstream consequences of genetic alterations on gene expression profiles [20].…”