PARP inhibitors: its role in treatment of cancer / 癌症
Chinese Journal of Cancer
;
(12): 463-471, 2011.
Article
in English
| WPRIM
| ID: wpr-294500
ABSTRACT
PARP is an important protein in DNA repair pathways especially the base excision repair (BER). BER is involved in DNA repair of single strand breaks (SSBs). If BER is impaired, inhibiting poly(ADP-ribose) polymerase (PARP), SSBs accumulate and become double stand breaks (DSBs). The cells with increasing number of DSBs become more dependent on other repair pathways, mainly the homologous recombination (HR) and the nonhomologous end joining. Patients with defective HR, like BRCA-deficient cell lines, are even more susceptible to impairment of the BER pathway. Inhibitors of PARP preferentially kill cancer cells in BRCA-mutation cancer cell lines over normal cells. Also, PARP inhibitors increase cytotoxicity by inhibiting repair in the presence of chemotherapies that induces SSBs. These two principles have been tested clinically. Over the last few years, excitement over this class of agents has escalated due to reported activity as single agent in BRCA1- or BRCA2-associated ovarian or breast cancers, and in combination with chemotherapy in triple negative breast cancer. This review covers the current results of clinical trials testing those two principles. It also evaluates future directions for the field of PARP inhibitor development.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Ovarian Neoplasms
/
Phthalazines
/
Piperazines
/
Benzamides
/
Benzimidazoles
/
Breast Neoplasms
/
Antineoplastic Combined Chemotherapy Protocols
/
Poly(ADP-ribose) Polymerases
/
Genes, BRCA1
/
Genes, BRCA2
Limits:
Female
/
Humans
Language:
English
Journal:
Chinese Journal of Cancer
Year:
2011
Type:
Article
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