Targeting fatty acid synthase: Potential for therapeutic intervention in Her-2/neu-overexpressing breast cancer

Javier A. Menendez, Ruth Lupu, Ramon Colomer

Research output: Contribution to journalReview article

63 Scopus citations

Abstract

Fatty acid synthase (FAS)-catalyzed de novo fatty acid biosynthesis, an anabolic energy-storage pathway largely considered of minor importance in humans, actively contributes to the cancer phenotype by virtue of its ability to specifically regulate the expression and activity of Her-2/neu (erbB-2) oncogene. First, a positive correlation between high levels of FAS expression and/or activity and the amplification and/or overexpression of Her-2/neu oncogene exists in human breast cancer cell lines. Second, Her-2/neu overexpression stimulates the activity of FAS gene promoter and ultimately mediates increased endogenous fatty acid biosynthesis, while this Her-2/neu-induced upregulation of breast cancer-associated FAS is inhibitable by anti-Her-2/neu antibodies such as trastuzumab (Herceptin™). Third, pharmacological inhibition of FAS activity negatively regulates the expression and tyrosine-kinase activity of Her-2/neu-coded p185Her-2/neu oncoprotein.

Original languageEnglish (US)
Pages (from-to)375-385
Number of pages11
JournalDrug News and Perspectives
Volume18
Issue number6
DOIs
StatePublished - Jul 1 2005

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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