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DNA Repair Proteins as Therapeutic Targets in Ovarian Cancer

Author(s):

Cesar Lopez-Camarillo*, Dolores Gallardo-Rincon, Erika Ruiz-Garcia, Horacio Astudillo de la Vega and Laurence A. Marchat   Pages 1 - 8 ( 8 )

Abstract:


Epithelial ovarian cancer is a serious public health problem worldwide with the highest mortality rate of all gynecologic cancers. The current standard-of-care for the treatment of ovarian cancer is based on chemotherapy based on adjuvant cisplatin/carboplatin and taxane regimens that represent the first-line agents for patients with advanced disease. The DNA repair activity of cancer cells determines the efficacy of anticancer drugs. These features make DNA repair mechanisms a promising target for novel cancer treatments. In this context a better understanding of the DNA damage response 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 will discuss the functions of DNA repair proteins and the advances in targeting DNA repair pathways with special emphasis in the inhibition of HRR and BER in ovarian cancer. We focused in the actual efforts in the development and clinical use of poly (ADPribose) polymerase (PARP) inhibitors for the intervention of BRCA1/BRCA2-deficient ovarian tumors. The clinical development of PARP inhibitors in ovarian cancer patients with germline BRCA1/2 mutations and sporadic high-grade serous ovarian cancer is ongoing. Some phase II and phase III trials have been completed with promising results for ovarian cancer patients.

Keywords:

Ovarian cancer, DNA repair, homologous recombination repair, base excision repair, poly (ADP-ribose) polymerase (PARP) inhibitors.

Affiliation:

Universidad Autónoma de la Ciudad de Mexico, Mexico. San Lorenzo 290. Col. del Valle. CP 03100. Mexico City, Laboratorio de Medicina Translacional. Instituto Nacional de Cancerología, Ciudad de México, Laboratorio de Medicina Translacional. Instituto Nacional de Cancerología, Ciudad de Mexico, Laboratorio de Investigación Translacional en Cáncer y Terapia Celular, Hospital de Especialidades Centro Médico Siglo XXI, Programa en Biomedicina Molecular y Red de Biotecnologia. Instituto Politecnico Nacional. Ciudad de Mexico



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