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urn:hdl:2445/198525 BRCA1 CpG island hypermethylation predicts sensitivity to poly(adenosine diphosphate)-ribose polymerase inhibitorsBRCA1 CpG island hypermethylation predicts sensitivity to poly(adenosine diphosphate)-ribose polymerase inhibitors Veeck, Jürgen Ropero, Santiago Setién, Fernando Gonzalez-Suarez, Eva Osorio, Ana Benitez, Javier Herman, James G. Esteller, Manel Proteïnes supressores de tumors ADN Malalties de l'ovari Genètica Tumor suppressor protein DNA Ovary diseases Genetics Recently, Fong et al reported the antitumor activity of the poly(adenosine diphosphate)-ribose polymerase (PARP) inhibitor olaparib (AZD2281; KU-0059436) in patients with BRCA1/BRCA2 germline mutated ovarian cancer. Female BRCA1 and BRCA2 mutation carriers have a significantly elevated lifetime risk of breast and ovarian cancer. BRCA1 and BRCA2 proteins play major roles in DNA double-strand break repair through homologous recombination, and inhibition of DNA single-strand break repair leads to the accumulation of double-strand breaks. These potentially lethal events in homologous recombination-deficient cells could be exploited for therapeutic purposes. The PARP-1 protein is essential for single-strand break repair, and inhibition of PARP leads to persistence of DNA lesions normally repaired by homologous recombination. 2023-05-26T13:20:03Z 2023-05-26T13:20:03Z 2010-10-10 2023-05-26T13:20:03Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.1200/JCO.2010.30.1010 Journal of Clinical Oncology, 2010, vol. 28, num. 29, p. e563-e564 https://doi.org/10.1200/JCO.2010.30.1010 (c) American Society of Clinical Oncology, 2010 info:eu-repo/semantics/openAccess American Society of Clinical Oncology Articles publicats en revistes (Ciències Fisiològiques)