Advisor(s)

Susan G. Powers-Lee

Contributor(s)

Wendy A. Smith, Gail S. Begley

Date of Award

2008

Date Accepted

10-2008

Degree Grantor

Northeastern University

Degree Level

M.S.

Degree Name

Master of Science

Department or Academic Unit

College of Arts and Sciences. Department of Biology.

Keywords

Biology, Cancer, Epidermal growth factor receptors

Subject Categories

Epidermal growth factor

Disciplines

Cancer Biology | Other Cell and Developmental Biology

Abstract

Epidermal growth factor receptor tyrosine kinase family members have distinct characteristics that specify their interactions and downstream signaling capabilities. In response to ligand, the receptors dimerize, resulting in activation of their kinase domains. Phosphorylation of specific C-terminal tyrosine residues specifies signal transduction pathways, resulting in mitogenic consequences for the cell. Epidermal growth factor receptors may translocate to the nucleus, initiating transcription. When epidermal growth factor receptors are dysregulated, aberrant signaling may result in cancer. Some factors that promote dysregulation are receptor overexpression and defects in negative regulation. A greater understanding of cancer therapeutics targeted to these receptors has been gained through crystal structures that elucidate ligand binding sites and dimerization contact points. Monoclonal antibodies and tyrosine kinase inhibitors targeted to epidermal growth factor receptors are approved for clinical use in advanced cancers, but show limited efficacy. New therapeutics target abnormal epidermal growth factor receptor activity by terminating receptor translation, uncoupling receptor accessory molecules, and restoring lost negative regulatory molecules. Most existing therapeutics target EGFR or HER2, leaving HER3 and HER4 therapeutics open for development.

Document Type

Master's Thesis

Rights Information

Copyright 2008

Rights Holder

Judy M. Richman


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