Development of 'synthetic lethal' strategies to target BRCA1-deficient breast cancer

Breast Cancer Res. 2009;11(5):108. doi: 10.1186/bcr2362.

Abstract

Recent clinical trials demonstrating the efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of BRCA1-deficient breast cancer have provided support for the 'synthetic lethal' concept of targeted cancer therapeutics. A new study provides further preclinical validation of this concept by demonstrating that BRCA1-deficient mouse mammary tumor cells are selectively sensitive to an inhibitor of the polycomb gene EZH2. The development of polycomb gene inhibitors may provide a novel approach to selectively exploit the molecular alterations in BRCA1-deficient breast tumors.

Publication types

  • Editorial
  • Comment

MeSH terms

  • Animals
  • BRCA1 Protein / deficiency*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics
  • DNA-Binding Proteins / antagonists & inhibitors
  • Enhancer of Zeste Homolog 2 Protein
  • Female
  • Histone-Lysine N-Methyltransferase / antagonists & inhibitors
  • Humans
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / enzymology
  • Mammary Neoplasms, Experimental / genetics
  • Mice
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Polycomb Repressive Complex 2
  • Transcription Factors / antagonists & inhibitors

Substances

  • BRCA1 Protein
  • DNA-Binding Proteins
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Transcription Factors
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Ezh2 protein, mouse
  • Histone-Lysine N-Methyltransferase
  • Polycomb Repressive Complex 2