Molecular and genetic bases of pancreatic cancer

Vanja Vaccaro, Alain Gelibter, Emilio Bria, Pierluigi Iapicca, Paola Cappello, Francesca Di Modugno, Maria Simona Pino, Carmen Nuzzo, Francesco Cognetti, Francesco Novelli, Paola Nisticò, Michele Milella

Research output: Contribution to journalArticlepeer-review

Abstract

Pancreatic cancer remains a formidable challenge for oncologists and patients alike. Despite intensive efforts, attempts at improving survival in the past 15 years, particularly in advanced disease, have failed. This is true even with the introduction of molecularly targeted agents, chosen on the basis of their action on pathways that were supposedly important in pancreatic cancer development and progression: indeed, with the notable exception of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, that has provided a minimal survival improvement when added to gemcitabine, other agents targeting EGFR, matrix metallo-proteases, farnesyl transferase, or vascular endothelial growth factor have not succeeded in improving outcomes over standard gemcitabine monotherapy for a variety of different reasons. However, recent developments in the molecular epidemiology of pancreatic cancer and an ever evolving understanding of the molecular mechanisms underlying pancreatic cancer initiation and progression raise renewed hope to find novel, relevant therapeutic targets that could be pursued in the clinical setting. In this review we focus on molecular epidemiology of pancreatic cancer, epithelial-to-mesenchymal transition and its influence on sensitivity to EGFR-targeted approaches, apoptotic pathways, hypoxia-related pathways, developmental pathways (such as the hedgehog and Notch pathways), and proteomic analysis as keys to a better understanding of pancreatic cancer biology and, most importantly, as a source of novel molecular targets to be exploited therapeutically.

Original languageEnglish
Pages (from-to)731-743
Number of pages13
JournalCurrent Drug Targets
Volume13
Issue number6
DOIs
Publication statusPublished - Jun 2012

Keywords

  • Pancreatic cancer
  • Signaling pathways
  • Targeted therapy

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

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