Epidermal Growth Factor Receptor in Pancreatic Cancer

Melissa Oliveira-Cunha,William G Newman,Ajith K Siriwardena

doi:10.3390/cancers3021513

Abstract

Pancreatic cancer is the fourth leading cause of cancer related death. The difficulty in detecting pancreatic cancer at an early stage, aggressiveness and the lack of effective therapy all contribute to the high mortality. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have demonstrated that EGFR is over-expressed in pancreatic cancer. Over-expression correlates with more advanced disease, poor survival and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway is an attractive therapeutic target. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis and regression in xenograft models, these benefits remain to be confirmed. Multimodality treatment incorporating EGFR-inhibition is emerging as a novel strategy in the treatment of pancreatic cancer.

Highlights

Carcinoma of the pancreas is an aggressive disease with a poor prognosis and an overall five-year survival rate of less than 3%, making it the fourth leading cause of cancer related mortality in the Western world [1]
The classical epidermal growth factor receptor (EGFR) receptor is known as HER-1 or ERBB-1 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 1) [6]
The intracellular domain of EGFR is activated upon ligand binding triggering the epidermal growth factor (EGF)-mediated tyrosine kinase signal transduction pathway (Figure 1) [9]

Summary

Introduction

Carcinoma of the pancreas is an aggressive disease with a poor prognosis and an overall five-year survival rate of less than 3%, making it the fourth leading cause of cancer related mortality in the Western world [1]. The dismal prognosis and the lack of effective therapeutic regimens for pancreatic cancer are related to several factors; in particular, pancreas cancer exhibits an aggressive biological phenotype characterized by early invasion of surrounding structures and rapid metastatic spread and is relatively resistant to radiation therapy and/or chemotherapy [3]. Much attention has been paid to the role of growth factors and growth factor receptors in pancreatic cancer. They have been implicated in carcinogenesis by affecting a variety of functions including cell proliferation, cell invasion and metastasis, angiogenesis, immune responsiveness and extracellular matrix formation. A number of growth factors and their receptors have been shown to play an important role in pancreatic cancer, including the epidermal growth factor (EGF) family. This family of ligands and receptors plays an important role in the pathogenesis of pancreatic ductal carcinoma and contributes to its aggressiveness [5]

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