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

J Nucl Med. 2017 Dec;58(12):1899-1903. doi: 10.2967/jnumed.117.198440. Epub 2017 Oct 19.

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 = 77) and PDA samples (n = 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, γ-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.

Keywords: biomarker; genetic profiling; pancreatic cancer; pancreatic ductal adenocarcinoma (PDA); targeted molecular imaging; targeted molecular therapy; theranostic approach.

MeSH terms

  • Biomarkers
  • Carcinoma, Pancreatic Ductal / diagnostic imaging*
  • Carcinoma, Pancreatic Ductal / therapy*
  • Cathepsins / genetics
  • Cathepsins / metabolism
  • Drug Delivery Systems
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mesothelin
  • Mucin-1 / genetics
  • Mucin-1 / metabolism
  • Pancreatic Neoplasms / diagnostic imaging*
  • Pancreatic Neoplasms / therapy*
  • Pathology, Molecular
  • RNA, Messenger / genetics
  • Theranostic Nanomedicine / methods*
  • Up-Regulation / genetics
  • gamma-Glutamyltransferase / genetics
  • gamma-Glutamyltransferase / metabolism

Substances

  • Biomarkers
  • GPI-Linked Proteins
  • MUC1 protein, human
  • Mucin-1
  • RNA, Messenger
  • gamma-Glutamyltransferase
  • Cathepsins
  • Mesothelin