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

Drug News Perspect. Jul-Aug 2005;18(6):375-85. doi: 10.1358/dnp.2005.18.6.927929.

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(TM)). Third, pharmacological inhibition of FAS activity negatively regulates the expression and tyrosine-kinase activity of Her-2/neu-coded p185(Her-2/neu) oncoprotein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • 4-Butyrolactone / administration & dosage
  • 4-Butyrolactone / analogs & derivatives
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / prevention & control
  • Catechin / administration & dosage
  • Catechin / analogs & derivatives
  • Cerulenin / administration & dosage
  • Drug Delivery Systems*
  • Fatty Acid Synthases / antagonists & inhibitors*
  • Fatty Acid Synthases / biosynthesis
  • Fatty Acid Synthases / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Lipid Metabolism / drug effects
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*

Substances

  • Antineoplastic Agents
  • Cerulenin
  • alpha-methylene gamma-butyrolactone
  • Catechin
  • epigallocatechin gallate
  • Fatty Acid Synthases
  • Receptor, ErbB-2
  • 4-Butyrolactone