Exploiting the Achilles heel of cancer: the therapeutic potential of poly(ADP-ribose) polymerase inhibitors in BRCA2-defective cancer

• Published in: British journal of radiology Vol. 81 Spec No 1; p. S6
• Main Authors: Kyle, S, Thomas, H D, Mitchell, J, Curtin, N J
• Format: Journal Article
• Language: English
• Published: England 01.10.2008
• Subjects: Animals; Azulenes - therapeutic use; Benzodiazepines - therapeutic use; BRCA2 Protein - deficiency; BRCA2 Protein - drug effects; DNA Breaks, Double-Stranded; DNA Breaks, Single-Stranded; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Female; Mice; Mice, Nude; Neoplasms, Experimental - drug therapy; Poly(ADP-ribose) Polymerase Inhibitors; Quinazolines - therapeutic use; Recombination, Genetic - drug effects

Poly(ADP-ribose) polymerase-1 (PARP-1) facilitates DNA single-strand break-base excision repair to maintain genomic stability. Inhibition or loss of PARP activity leads to a recombinogenic phenotype characterized by increased sister chromatid exchange. Deficiency in homologous recombination (HR) owi...