César López-Camarillo*, Dolores G. Rincón, Erika Ruiz-García, Horacio Astudillo-de la Vega and Laurence A. Marchat Pages 316 - 323 ( 8 )
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.
Ovarian cancer, DNA repair, homologous recombination repair, base excision repair, poly (ADP-ribose) polymerase (PARP) inhibitors.
Posgrado en Ciencias Genomicas, Universidad Autonoma de la Ciudad de Mexico, México City, Laboratorio de Medicina Translacional. Instituto Nacional de Cancerologia, Ciudad de Mexico, Laboratorio de Medicina Translacional. Instituto Nacional de Cancerologia, Ciudad de Mexico, Laboratorio de Investigacion Translacional en Cancer y Terapia Celular, Hospital de Oncologia Centro Medico Nacional Siglo XXI, Programa en Biomedicina Molecular y Red de Biotecnologia. Instituto Politecnico Nacional. Ciudad de Mexico