Trastuzumab: Mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer

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Abstract

Trastuzumab is a humanized mAb directed against the extracellular domain of the tyrosine kinase receptor HER2. Trastuzumab has shown clinical activity in HER2-overexpressing breast cancers and, at present, is currently approved for patients whose tumours have this abnormality, in both the metastatic and the adjuvant setting. Several issues about its optimal use, however, are still unresolved. One of the reasons for these uncertainties lies in the absence of conclusive data about its mechanism of action and possible primary or acquired resistance mechanisms. Therefore, clinical questions such as how to optimize patient selection, how to prevent resistance to trastuzumab, or what is the optimal management of those patients whose tumours progress during treatment still await convincing answers. This review summarises the current knowledge on the preclinical and clinical evidence about the mechanism of action of trastuzumab and on the mechanisms underlying the development of resistance and also briefly discusses their possible clinical implications.

Original languageEnglish
Pages (from-to)977-984
Number of pages8
JournalAnnals of Oncology
Volume18
Issue number6
DOIs
Publication statusPublished - Jun 2007

Keywords

  • Breast neoplasms
  • HER2
  • Mechanism of action
  • Resistance
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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