title: Targeting Tankyrase 1 as a therapeutic strategy for BRCA-associated cancer.
abstract: The BRCA1 and BRCA2 proteins are involved in the maintenance of genome stability and germ-line loss-of-function mutations in either BRCA1 or BRCA2 strongly predispose carriers to cancers of the breast and other organs. It has been demonstrated previously that inhibiting elements of the cellular DNA maintenance pathways represents a novel therapeutic approach to treating tumors in these individuals. Here, we show that inhibition of the telomere-associated protein, Tankyrase 1, is also selectively lethal with BRCA deficiency. We also demonstrate that the selectivity caused by inhibition of Tankyrase 1 is associated with an exacerbation of the centrosome amplification phenotype associated with BRCA deficiency. We propose that inhibition of Tankyrase 1 could be therapeutically exploited in BRCA-associated cancers.
authors.affiliation: Cancer Research UK Gene Function and Regulation Group, Institute of Cancer Research, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: McCabe
authors.forename: M A
authors.initials: MA
authors.lastname: Cerone
authors.forename: T
authors.initials: T
authors.lastname: Ohishi
authors.forename: H
authors.initials: H
authors.lastname: Seimiya
authors.forename: C J
authors.initials: CJ
authors.lastname: Lord
authors.forename: A
authors.initials: A
authors.lastname: Ashworth
mesh_terms: D018385:Centrosome / Q000502:physiology; D005784:Gene Amplification; D020868:Gene Silencing; D019398:Genes, BRCA1 / Q000502:physiology*; D024522:Genes, BRCA2 / Q000502:physiology*; D045325:HCT116 Cells; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D038501:Tankyrases / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D038501:Tankyrases; C418109:TNKS protein, human