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The Molecular and Cellular Biology of HER2/neu Gene Amplification/Overexpression and the Clinical Development of Herceptin (Trastuzumab) Therapy for Breast Cancer

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Book cover Advances in Breast Cancer Management

Part of the book series: Cancer Treatment and Research ((CTAR,volume 103))

Abstract

Proto oncogenes represent a family of genes which when activated have been shown to play a role in the pathogenesis of a number of malignancies in vertebrate species including humans.1,2 In physiologic states these same genes are known to play a role in the normal cell growth control and differentiation. The HER2/neu gene is a member of the Type I receptor tyrosine kinase (RTK) group which is one of the subfamilies in the proto oncogene family and encodes a 185kD surface membrane receptor protein. This gene has been localized to chromosome 17q21,1 and the encoded protein is expressed in a wide variety of tissues including the skin, oral mucera, breast, ovary, endometrium, lung, liver, pancreas, small and large bowel, kidney, bladder and the central nervous system as well as some connective tissues.4–5 The exact physiological role of the HER2/neu protein in these tissues is not completely understood, but like other proto oncogenes it is believed to play an important signaling role in cellular proliferation and differentiation processes. Current data suggests that it forms hetero-dimers with other members of the RTKI family (such as HER 1, HER3 and HER4 in response to various ligands known as heregulins.6–8 Activation of HER2/neu results in an increase its kinase activity which in turn initiates signal transduction resulting in either cellular proliferation and/or differentiation, depending on the ligand as well as the conditions.9–14 In human breast cancers, a non-inherited alteration occurs in this gene in 25–30% of cases.

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Authors and Affiliations

  1. Division of Hematology Oncology, UCLA School of Medicine, USA

    Mark D. Pegram M.D. (Adjunct Assistant Professor of Medicine), Gottfried Konecny M.D. (Post-Graduate Research Fellow) & Dennis J. Slamon M.D. (Professor and Chief)

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  1. Mark D. Pegram M.D.
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  2. Gottfried Konecny M.D.
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  3. Dennis J. Slamon M.D.
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Editors and Affiliations

  1. Breast Medical Oncology, Division of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, 676 North St. Clair Street, Suite 850, 60611-2927, Chicago, IL, USA

    William J. Gradishar M.D. (Associate Professor of Medicine, Director) (Associate Professor of Medicine, Director)

  2. Cancer Center, Department of Surgery, Emory University School of Medicine, 1364 Clifton Road, N.E., Suite B206, 30322-1104, Atlanta, GA, USA

    William C. Wood M.D. (Joseph Brown Whitehead Professor and Chairman, Clinical Director) (Joseph Brown Whitehead Professor and Chairman, Clinical Director)

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Pegram, M.D., Konecny, G., Slamon, D.J. (2000). The Molecular and Cellular Biology of HER2/neu Gene Amplification/Overexpression and the Clinical Development of Herceptin (Trastuzumab) Therapy for Breast Cancer. In: Gradishar, W.J., Wood, W.C. (eds) Advances in Breast Cancer Management. Cancer Treatment and Research, vol 103. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-3147-7_4

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  • DOI: https://doi.org/10.1007/978-1-4757-3147-7_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-3149-1

  • Online ISBN: 978-1-4757-3147-7

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