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

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.

• Authors: Max S Wicha
• Journal: Breast cancer research : BCR (Breast Cancer Res) Vol. 11 Issue 5 Pg. 108 ( 2009) ISSN: 1465-542X [Electronic] England
• PMID: 19804613 (Publication Type: Editorial, Comment)

Chemical References

• 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

Topics

• Animals
• BRCA1 Protein (deficiency)
• Breast Neoplasms (drug therapy, enzymology, 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, enzymology, genetics)
• Mice
• Poly(ADP-ribose) Polymerase Inhibitors
• Polycomb Repressive Complex 2
• Transcription Factors (antagonists & inhibitors)