Unraveling the biologic and clinical complexities of HER2

John Park, Richard Neve, J. Szöllősi, Christopher Benz

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

It has been over 20 years since the discovery of the human epidermal growth factor receptor 2 (HER2), a tyrosine kinase receptor that is a potent oncoprotein in breast and other cancers and has become an opportune target for therapy. HER2 plays a critical role in normal development, forming homodimers or heterodimers with other HER family members and triggering downstream signaling cascades controlling proliferation, cell survival, and apoptosis. However, amplification of the HER2 gene in cancer cells results in overexpression of HER2 receptors on the cell surface, leading to excessive and dysregulated signaling. HER2-driven signaling also upregulates transcription factors that act on the HER2 promoter, increasing its expression. In breast cancer, HER2 is gene amplified in 20%-25% of primary tumors and is associated with a more aggressive phenotype and poorer prognosis. The key role HER2 plays in tumorigenesis makes it an ideal target for therapy. Trastuzumab, a monoclonal antibody against HER2, inhibits downstream signaling and has proven to be effective against HER2-overexpressing metastatic breast cancer both as a single agent and in combination with chemotherapy. Seminal clinical trial data also show that the use of adjuvant trastuzumab in combination with chemotherapy or as a single agent after chemotherapy significantly increases disease-free and overall survival. Lapatinib, a dual tyrosine kinase inhibitor against HER1 and HER2, has been approved in combination with capecitabine for HER2-overexpressing advanced or metastatic breast cancer, which has progressed following previous anthracycline, taxane, and trastuzumab therapy. Other HER2-targeting strategies are also under active investigation.

Original languageEnglish
Pages (from-to)392-401
Number of pages10
JournalClinical Breast Cancer
Volume8
Issue number5
DOIs
Publication statusPublished - Oct 1 2008

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Breast Neoplasms
Combination Drug Therapy
human ERBB2 protein
erbB-1 Genes
Anthracyclines
Oncogene Proteins
Receptor Protein-Tyrosine Kinases
Cell Surface Receptors
Protein-Tyrosine Kinases
Disease-Free Survival
Neoplasms
Cell Survival
Carcinogenesis
Transcription Factors
Up-Regulation
Therapeutics
Monoclonal Antibodies
Clinical Trials
Apoptosis
Phenotype

Keywords

  • ErbB2
  • Lapatinib
  • Metastatic disease
  • Monoclonal antibody
  • Trastuzumab

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Unraveling the biologic and clinical complexities of HER2. / Park, John; Neve, Richard; Szöllősi, J.; Benz, Christopher.

In: Clinical Breast Cancer, Vol. 8, No. 5, 01.10.2008, p. 392-401.

Research output: Contribution to journalArticle

Park, John ; Neve, Richard ; Szöllősi, J. ; Benz, Christopher. / Unraveling the biologic and clinical complexities of HER2. In: Clinical Breast Cancer. 2008 ; Vol. 8, No. 5. pp. 392-401.
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