Title:Molecular and Genetic Bases of Pancreatic Cancer
VOLUME: 13 ISSUE: 6
Author(s):Vanja Vaccaro, Alain Gelibter, Emilio Bria, Pierluigi Iapicca, Paola Cappello, Francesca Di Modugno, Maria Simona Pino, Carmen Nuzzo, Francesco Cognetti, Francesco Novelli, Paola Nistico and Michele Milella
Affiliation:Medical Oncology A, Regina Elena National Cancer Institute, Via Elio Chianesi, 53, 00144 Rome, Italy.
Keywords:Pancreatic cancer, signaling pathways, targeted therapy, genetic, META-ANALYSIS, RANDOMIZED TRIALS, Inherited Cancer Syndromes, EGFR PATHWAY, PROTEOMICS, TRAIL
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.
