Development of 'synthetic lethal' strategies to target BRCA1-deficient breast cancer.
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.
Wicha
Max S
MS
D000818:Animals; D019313:BRCA1 Protein / Q000172:deficiency*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D051379:Mice; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D063151:Polycomb Repressive Complex 2; D014157:Transcription Factors / Q000037:antagonists & inhibitors
D019313:BRCA1 Protein; D004268:DNA-Binding Proteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2