Epidermal growth factor and Transforming growth factor α motogenic activities are mediated by Epidermal growth factor receptor : Identification of signalling pathways involved in head and neck cancer
type: CreativeWork
description: Background: The alteration of Epidermal Growth Factor Receptor (EGFR) plays a major role in the development of Head and Neck cancer. However, the only FDA approved EGFR target for this neoplasm is the drug Cetuximab. Cetuximab can only be used where there is an over-expression of EGFR. Cetuximab works by competing with the ligands Epidermal Growth Factor (EGF) and Transforming Growth Factor alpha (TGFα) to bind the extracellular domain of EGFR. Inhibition of this ligand binding blocks the activation of subsequent signalling pathways. It is known that not all Head and Neck cancers over-expressing EGFR respond to Cetuximab. It has been postulated that some of these tumours have additional genetic lesions. Resistance to Cetuximab has been associated with the genetic lesions to EGFR mutation and Ras mutations. These mutations are more common in Asian than Caucasian patients. More recently the Tyrosine kinase inhibitors (Gefitinib and Erlotinib) have been investigated as drugs to target tumours with EGFR mutation. These inhibitors bind to the cytoplasmic domain of the EGFR and compete with ATP and inhibit phosphorylation of the receptor. Another inhibitor of interest is PD98509 which is a selective ERK1/2 inhibitor and may be used in targeting tumours with a Ras mutation. None of these inhibitors has received FDA approval for Head and Neck cancer treatment. Aim: The main aims of the project were to investigate the effect of the growth factors EGF and TGFα and the inhibitors; Gefitinib, Erlotinib and PD98059 on cancer cell lines obtained from Asian head and neck cancer patients. The first area of study was to investigate the effect of the growth factors EGF and TGFα on cell proliferation, morphological changes, EMT marker expression, single cell migration and collective cell migration. Once the initial data had been collected a second part was to determine whether the inhibitors; Gefitinib, Erlotinib and PD98059 could block the stimulatory effect of EGF and TGFα in these …
abstract: Background: The alteration of Epidermal Growth Factor Receptor (EGFR) plays a major role in the development of Head and Neck cancer. However, the only FDA approved EGFR target for this neoplasm is the drug Cetuximab. Cetuximab can only be used where there is an over-expression of EGFR. Cetuximab works by competing with the ligands Epidermal Growth Factor (EGF) and Transforming Growth Factor alpha (TGFα) to bind the extracellular domain of EGFR. Inhibition of this ligand binding blocks the activation of subsequent signalling pathways. It is known that not all Head and Neck cancers over-expressing EGFR respond to Cetuximab. It has been postulated that some of these tumours have additional genetic lesions. Resistance to Cetuximab has been associated with the genetic lesions to EGFR mutation and Ras mutations. These mutations are more common in Asian than Caucasian patients. More recently the Tyrosine kinase inhibitors (Gefitinib and Erlotinib) have been investigated as drugs to target tumours with EGFR mutation. These inhibitors bind to the cytoplasmic domain of the EGFR and compete with ATP and inhibit phosphorylation of the receptor. Another inhibitor of interest is PD98509 which is a selective ERK1/2 inhibitor and may be used in targeting tumours with a Ras mutation. None of these inhibitors has received FDA approval for Head and Neck cancer treatment. Aim: The main aims of the project were to investigate the effect of the growth factors EGF and TGFα and the inhibitors; Gefitinib, Erlotinib and PD98059 on cancer cell lines obtained from Asian head and neck cancer patients. The first area of study was to investigate the effect of the growth factors EGF and TGFα on cell proliferation, morphological changes, EMT marker expression, single cell migration and collective cell migration. Once the initial data had been collected a second part was to determine whether the inhibitors; Gefitinib, Erlotinib and PD98059 could block the stimulatory effect of EGF and TGFα in these …
author: Thwe, Aye Myat
language: eng
date published: 2020
date modified: 2026-07-24T02:08:52Z
provider: University of Dundee
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Dundee