DNA repair as a novel therapeutic target in breast cancer

César López-Camarillo, Laurence A. Marchat, Sergio Rodríguez-Cuevas, Elena Arechaga, Carlos Pérez-Plascencia, Elizabeth J.Castañeda Ortiz, Miguel A. Fonseca

Producción científica: Capítulo del libro/informe/acta de congresoCapítulorevisión exhaustiva

Resumen

DNA repair mechanisms are key events in the maintenance of DNA integrity and genome stability. The cellular response to DNA damage consists in the activity of biological conserved pathways including homologous recombination repair (HRR), non-homologous end-joining (NHEJ), base excision repair (BER), mismatch repair (MMR), nucleotide excision repair (NER), and direct repair (DR) that operate in a concerted way to minimize genetic information loss resulting from different DNA lesions. Notably, DNA repair mechanisms are frequently deregulated in cancer. In tumor cells, increased DNA repair and increased levels of DNA repair proteins have been associated with resistance to treatment to anticancer agents acting as DNA-damaging agents. In contrast, defects in DNA repair pathways resulting from somatic or inherited mutations in DNA repair genes result in a hypersensitivity to these drugs. Therefore, effectiveness of chemotherapeutic agents and ionizing radiations that act causing extensive DNA damage is largely influenced by DNA repair pathways. In this context, a better understanding of the DNA damage caused by antitumor agents has provided the basis for the use of DNA repair inhibitors to improve the therapeutic use of DNA-damaging drugs. In this review, we discuss the current approaches that are currently under clinical investigation in breast cancer. We described the recent advances targeting DNA repair pathways with special emphasis in the inhibition of HRR involved in repair of DNA double-strand breaks, as well as in the development of Poly(ADP-ribose) polymerase (PARP) inhibitors and intervention of BRCA1/BRCA2-deficient tumors.

Idioma originalInglés
Título de la publicación alojadaDNA Repair
Subtítulo de la publicación alojadaNew Research
EditorialNova Science Publishers, Inc.
Páginas51-78
Número de páginas28
ISBN (versión impresa)9781621007562
EstadoPublicada - ene. 2012
Publicado de forma externa

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