6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance.

Journal article

Familial breast and ovarian cancers are often defective in homologous recombination (HR) due to mutations in the BRCA1 or BRCA2 genes. Cisplatin chemotherapy or poly(ADP-ribose) polymerase (PARP) inhibitors were tested for these tumors in clinical trials. In a screen for novel drugs that selectively kill BRCA2-defective cells, we identified 6-thioguanine (6TG), which induces DNA double-strand breaks (DSB) that are repaired by HR. Furthermore, we show that 6TG is as efficient as a PARP inhibit...

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Authors: Issaeva, N; Thomas, H; Djureinovic, T; Djurenovic, T; Jaspers, J

• Publication status: Published
• Journal: Cancer research
• Volume: 70
• Issue: 15
• Pages: 6268-6276
• Publication date: 2010-08-01
• DOI: 10.1158/0008-5472.can-09-3416
• EISSN: 1538-7445
• ISSN: 0008-5472
• Language: English
• Keywords: Humans; Genes, BRCA2; Poly(ADP-ribose) Polymerases; Enzyme Inhibitors; Base Pair Mismatch; DNA Repair; BRCA2 Protein; HCT116 Cells; Thioguanine; Mice; Mammary Neoplasms, Experimental; Animals; P-Glycoprotein; Antimetabolites, Antineoplastic; Drug Synergism; Apoptosis Regulatory Proteins; Colonic Neoplasms