TY - JOUR
T1 - The potential for poly (ADP-ribose) polymerase inhibitors in cancer therapy
AU - Javle, M.
AU - Curtin, N. J.
PY - 2011/11
Y1 - 2011/11
N2 - The modulation of DNA repair pathways for therapeutic benefit in cancer has now become a reality with the development of poly (ADP-ribose) polymerase inhibitors (PARPi). PARP is involved in single-strand DNA breaks, which in the presence of defective homologous recombination repair lead to double-strand DNA breaks, the most lethal form of DNA damage. These agents therefore may be the drugs of choice for BRCA mutant breast and ovarian cancers. PARPi result in synergistic antitumor effects when combined with cisplatin, temozolomide, topoisomerase inhibitors and ionizing radiation. The indications for PARPi lie beyond BRCA mutations and may include genomic and functional defects in DNA repair and damage response pathways. Several PARPi are in the clinical development phase at this time and, given the recent failure of a phase III clinical trial of iniparib in triple-negative breast cancer, the identification of structural and functional differences between these inhibitors becomes critical. Acquired resistance to PARPi is being noted and represents an important limitation in this field. A concise review of the literature in this field is presented.
AB - The modulation of DNA repair pathways for therapeutic benefit in cancer has now become a reality with the development of poly (ADP-ribose) polymerase inhibitors (PARPi). PARP is involved in single-strand DNA breaks, which in the presence of defective homologous recombination repair lead to double-strand DNA breaks, the most lethal form of DNA damage. These agents therefore may be the drugs of choice for BRCA mutant breast and ovarian cancers. PARPi result in synergistic antitumor effects when combined with cisplatin, temozolomide, topoisomerase inhibitors and ionizing radiation. The indications for PARPi lie beyond BRCA mutations and may include genomic and functional defects in DNA repair and damage response pathways. Several PARPi are in the clinical development phase at this time and, given the recent failure of a phase III clinical trial of iniparib in triple-negative breast cancer, the identification of structural and functional differences between these inhibitors becomes critical. Acquired resistance to PARPi is being noted and represents an important limitation in this field. A concise review of the literature in this field is presented.
KW - BRCA2 gene
KW - DNA repair-deficiency disorders
KW - poly (ADP-ribose) polymerases
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U2 - 10.1177/1758834011417039
DO - 10.1177/1758834011417039
M3 - Review article
C2 - 22084640
AN - SCOPUS:84856889082
SN - 1758-8340
VL - 3
SP - 257
EP - 267
JO - Therapeutic Advances in Medical Oncology
JF - Therapeutic Advances in Medical Oncology
IS - 6
ER -