Primary trastuzumab resistance

New tricks for an old drug

Jason A. Wilken, Nita Jane Maihle

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Trastuzumab is the first Food and Drug Administration (FDA)-approved therapeutic targeting a HER-family receptor tyrosine kinase (HER2/ErbB2/neu). Although trastuzumab is effective in the treatment of HER2-positive breast cancer, a substantial proportion of patients will not respond to trastuzumab-based regimens (primary resistance), and those who do respond will often lose clinical benefits (i.e., secondary resistance). Although multiple mechanisms underlying the development of secondary trastuzumab resistance have been identified, few studies have specifically examined the basis of primary trastuzumab resistance. Here, we review these studies, which together demonstrate that trastuzumab induces phenotypic changes in tumor cells, even when they are not growth inhibited by trastuzumab, including changes in gene expression. These changes have important clinical implications, including the sensitization of malignant cells to other therapeutic drugs. In light of these observations, we propose that the conventional definition of resistance as it pertains to trastuzumab and, perhaps, to other targeted therapeutics, may require revision. The results of these studies will be useful in informing the direction of future basic and clinical research focused on overcoming primary trastuzumab resistance.

Original languageEnglish (US)
Pages (from-to)53-65
Number of pages13
JournalAnnals of the New York Academy of Sciences
Volume1210
Issue number1
DOIs
StatePublished - Jan 1 2010

Fingerprint

Pharmaceutical Preparations
Trastuzumab
Drugs
Trick
United States Food and Drug Administration
Therapeutics
Gene expression
Protein-Tyrosine Kinases
Tumors
Cells
Breast Neoplasms
Gene Expression
Growth
Research
Neoplasms
Informing
Food and Drug Administration
Sensitization
Breast Cancer
Clinical Research

Keywords

  • Breast cancer
  • EGFR/ErbB/HER
  • Primary resistance
  • Targeted therapeutics
  • Trastuzumab/herceptin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Primary trastuzumab resistance : New tricks for an old drug. / Wilken, Jason A.; Maihle, Nita Jane.

In: Annals of the New York Academy of Sciences, Vol. 1210, No. 1, 01.01.2010, p. 53-65.

Research output: Contribution to journalArticle

Wilken, Jason A. ; Maihle, Nita Jane. / Primary trastuzumab resistance : New tricks for an old drug. In: Annals of the New York Academy of Sciences. 2010 ; Vol. 1210, No. 1. pp. 53-65.
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