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The ErbB2 Signaling Network as a Target for Breast Cancer Therapy

  • Ali Badache
  • Anthony Gonçalves
Article

Abstract

Overexpression of the ErbB2/Her2 receptor tyrosine kinase in breast cancers is associated with the most aggressive tumors. Experimental studies have revealed that ErbB2 shows many features of a therapeutic target: ErbB2 is able to confer many of the characteristics of a cancerous cell, including uncontrolled proliferation, resistance to apoptosis and increased motility; ErbB2 overexpression is specific to tumor cells; as a cell surface-associated protein, it is easily accessible to drugs and as a kinase it is amenable to targeted inhibition by small molecules. Recent clinical results demonstrate the efficacy of ErbB2-targeting therapy and promise an expanding use of ErbB2-targeting drugs for breast cancer treatment. However, as only a fraction of patients responds successfully to therapy and risks of recurrence are still high, further investigation is required for an improved understanding of the complex network of signaling pathways underlying ErbB2-driven cancer progression.

Keywords

ErbB2/HER2/Neu Breast cancer Signaling Cancer therapy Trastuzumab 

Abbreviations

ADCC

antibody dependent cellular toxicity

Cox

cyclooxygenase

EGF

epidermal growth factor

HAS

Her2-associated sequence

iNOS

nitric oxide synthase

NRG

neuregulin

PLCγ

phospholipase Cγ

TGF

transforming growth factor

Notes

Acknowledgments

We would like to apologize to our many colleagues whose important work regarding ErbB2 could not be referred to, because of space limitations. We would like to thank Nancy Hynes and Sandra Aresta for critical reading of the manuscript. We thank Daniel Birnbaum, Jean-Paul Borg, Françoise Birg, Claude Mawas, Patrice Viens and Dominique Maraninchi for their support. AB is supported by the Avenir program of Inserm, Fondation de France, Fondation pour la Recherche Médicale, Ligue Nationale contre la Cancer and Conseil général des Bouches-du-Rhône. AG and AB are supported by the Institut National du Cancer (INCa—Canceropôle PACA).

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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  1. 1.UMR599 InsermCentre de Recherche en Cancérologie de MarseilleMarseilleFrance
  2. 2.Département d’oncologie médicaleInstitut Paoli-CalmettesMarseilleFrance
  3. 3.Faculté de médecineUniversité de la MéditerranéeMarseilleFrance
  4. 4.Institut Paoli-CalmettesMarseilleFrance
  5. 5.Université de la MéditerranéeMarseilleFrance

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