Data driven prioritization and review of targets for molecular based theranostic approaches in pancreatic cancer.
J Nucl Med. 2017 Oct 19. pii: jnumed.117.198440. doi: 10.2967/jnumed.117.198440. [Epub ahead of print]
# contributed equally
Koller M, Hartmans E, de Groot DJA, Zhao XJ, van Dam GM, Nagengast WB#, Fehrmann RSN#
Molecular targeted therapeutical 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 = 77) and PDA samples (n = 103). Functional Genomic mRNA (FGmRNA) profiling was applied to predict target upregulation on the protein level. We prioritized these targets based on current status of (pre)-clinical therapeutical and imaging evaluation in PDA. Results: We identified 213 significantly upregulated proteins in PDA compared to normal pancreatic tissue. We prioritized mucin-1 (MUC1), mesothelin (MSLN), gamma-glutamyltransferase 5 (GGT5) and cathepsin-E (CTSE) as the most interesting targets, since studies already demonstrated their potential for both therapeutic and imaging strategies in literature. Conclusion: This study can facilitate clinicians and drug developers in deciding which theranostic targets should be taken for further clinical evaluation in PDA.