Title:Targeting EGFR in Pancreatic Cancer Treatment
Volume: 13
Issue: 6
Author(s): T. Troiani, E. Martinelli, A. Capasso, F. Morgillo, Michele Orditura, F. De Vita and F. Ciardiello
Affiliation:
Keywords:
Pancreatic cancer, EGFR-targeted therapy, cetuximab, erlotinib, chemotherapy, targeted therapy, signaling disorder, onconeogenesis, clinical trials, EGFR, mutations
Abstract: The prognosis of patients with pancreatic cancer is extremely poor, and current systemic therapies provide
marginal survival benefits for treated patients. The era of targeted therapies has offered a new avenue to search for
potentially more effective strategies. Epidermal growth factor receptor (EGFR) is a member of the erbB/human epidermal
growth factor receptor family of tyrosine kinases, which includes erbB2/HER2, erbB3/HER3 and erbB4/HER4.
Epidermal growth factor receptor overexpression may be detected in up to 90% of pancreatic tumors. Two pharmacologic
approaches have been successfully used to inhibit epidermal growth factor receptor function in cancer treatment:
neutralizing monoclonal antibodies and small molecule tyrosine inhibitors. The randomized trials studying the addition of
EGFR targeted agents to gemcitabine compared with gemcitabine alone have been disappointing, although results with
the EGFR tyrosine kinase inhibitor erlotinib were statistically significant but clinically of marginal benefit. In this article,
we review the epidermal growth factor receptor signaling network in pancreatic cancer, the strategies to increase the
effectiveness of epidermal growth factor receptor inhibitors, and the clinical trials of these inhibitors in pancreatic cancer.