The ErbB Receptors and their Ligands in Cancer: An Overview

Abstract

This review article provides an overview on the most recent advances on the role of ErbB receptors and growth factors of the epidermal growth factor (EGF)-family of peptides in cancer pathogenesis and progression. The ErbB tyrosine kinases and the EGF-like peptides form a complex system. In fact, the interactions occurring between receptors and ligands of these families affect the type and the duration of the intracellular signals that derive from receptor activation. Interestingly, activation of ErbB receptors is also driven by different classes of membrane receptor, suggesting that ErbB kinases can amplify growth promoting signals carried by different pathways. The importance of ErbB receptors and EGF-like peptides in development of organs and tissues has been demonstrated by using different mouse models. In vitro and in vivo studies have also shown that ErbB receptors and their ligands can act as transforming genes. However, evidence suggests that cooperation of different receptors and ligands is necessary to induce a fully transformed phenotype. Indeed, co-expression of different ErbB receptors and EGF-like growth factors is a common phenomenon in human primary carcinomas. This observation suggests that the growth and the survival of carcinoma cells is sustained by a network of receptors/ligands of the ErbB family. In this respect, the contemporary expression of different ErbB tyrosine kinases and/or EGF-like growth factors in human carcinomas might also affect tumor response to target based agents directed against the ErbB receptor/ligand system.

A functional epidermal growth factor (EGF) polymorphism, EGF serum levels and renal cell carcinoma risk in a Chinese population

“…DISCUSSION EGF, a potent mitogenic peptide, is a growth factor that activates a signaling transduction cascade responsible for activating genes involved in cell proliferation, differentiation or survival through binding to its receptor (EGFR), 16 having an important role in carcinogenesis. 17 Therefore, genetic variant in the EGF gene was hypothesized to have a critical role in tumorigenesis. In this study, we analyzed the association between a functional G61A polymorphism of EGF and the risk for developing RCC in a Chinese population.…”

Heterogeneity of ERBB2 amplification in adenocarcinoma, squamous cell carcinoma and large cell undifferentiated carcinoma of the lung

“…[1][2][3] The ERBB2 gene product HER2 is the target of an antibody-based therapy (trastuzumab), which has been shown to be remarkably effective in both the metastatic and adjuvant setting for HER2-positive breast cancer [4][5][6] and in advanced HER2-positive gastric cancer. 7 Moreover, with the tyrosine kinase inhibitor lapatinib which targets both EGFR and HER2 an alternative option for HER2-positive breast cancers has been introduced 8 and is under analysis for other tumor types.…”

Targeted therapy in non-small cell lung cancer

“…The signal is passed along various downstream pathways. The most relevant seem to be the RAS/RAF/ MEK/MAPK pathway, the PI3K/AKT pathway and the STAT3/STAT5 pathway [8]. These pathways lead to changes in gene transcription and alterations in the cell cycle, resulting in increased cell proliferation and angiogenesis, inhibition of apoptosis and changes in their capacity for migration, adhesion and invasion.…”