TY - JOUR
T1 - DNA repair proteins as therapeutic targets in ovarian cancer
AU - López-Camarillo, César
AU - G. Rincón, Dolores
AU - Ruiz-García, Erika
AU - Vega, Horacio Astudillo de la
AU - Marchat, Laurence A.
N1 - Publisher Copyright:
© 2019 Bentham Science Publishers.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Base excision repair
KW - DNA repair
KW - Homologous recombination repair
KW - Ovarian cancer
KW - Poly (ADP-ribose) polymerase (PARP) inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85062092628&partnerID=8YFLogxK
U2 - 10.2174/1389203719666180914091537
DO - 10.2174/1389203719666180914091537
M3 - Artículo
C2 - 30215333
SN - 1389-2037
VL - 20
SP - 316
EP - 323
JO - Current Protein and Peptide Science
JF - Current Protein and Peptide Science
IS - 4
ER -