Emerging pathways and future targets for the molecular therapy of pancreatic cancer

Vanja Vaccaro, Davide Melisi, Emilio Bria, Federica Cuppone, Ludovica Ciuffreda, Maria Simona Pino, Alain Gelibter, Giampaolo Tortora, Francesco Cognetti, Michele Milella

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Pancreatic cancer treatment remains a challenge for clinicians and researchers. Despite undisputable advances in the comprehension of the molecular mechanisms underlying cancer development and progression, early disease detection and clinical management of patients has made little, if any, progress in the past 20 years. Clinical development of targeted agents directed against validated pathways, such as the EGF/EGF receptor axis, the mutant KRAS protein, MMPs, and VEGF-mediated angiogenesis, alone or in combination with gemcitabine-based standard chemotherapy, has been disappointing. Areas covered: This review explores the preclinical rationale for clinical approaches aimed at targeting the TGF-β, IGF, Hedgehog, Notch and NF-κB signaling pathways, to develop innovative therapeutic strategies for pancreatic cancer. Expert opinion: Although some of the already clinically explored approaches (particularly EGFR and KRAS targeting) deserve further clinical consideration, by employing more innovative and creative clinical trial designs than the gemcitabinetargeted agent paradigm that has thus far invariably failed, the targeting of emerging and relatively unexplored signaling pathways holds great promise to increase our understanding of the complex molecular biology and to advance the clinical management of pancreatic cancer.

Original languageEnglish
Pages (from-to)1183-1196
Number of pages14
JournalExpert Opinion on Therapeutic Targets
Volume15
Issue number10
DOIs
Publication statusPublished - Oct 2011

Keywords

  • molecular pathways
  • pancreatic cancer
  • targeted therapy

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

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