Poly(ADP-Ribose) polymerase 1: a therapeutic hope in gynecologic cancers.
نویسندگان
چکیده
The Poly(ADP-ribose) polymerase-1 (PARP1) is a multifunctional nuclear protein involved in a variety of cellular functions. Recently, its role in the onset, progression and therapy resistance of cancers in general and reproductive cancers in particular has been recognised. The PARP associated signaling is perceived to play a key role in the development, sustenance and relapse of reproductive cancers. This has led to the preclinical and clinical assessment of PARP inhibitors as targeted therapeutic agents in reproductive cancers. In the first part of this review, we have summarized the current status of PARP in the onset, progression and therapy resistance of reproductive cancers. In the second part of the review, we have discussed the translational applications of PARP inhibitors, underscoring the perceived therapeutic opportunities, bottlenecks and the utility of the ongoing clinical trials.
منابع مشابه
Phosphorylation of ribosomal protein S6 confers PARP inhibitor resistance in BRCA1-deficient cancers
Inhibition of poly(ADP-ribose) polymerase (PARP) is a promising therapeutic strategy for BRCA1 deficient cancers, however, the development of drug resistance limits clinical efficacy. Previously we found that the BRCA1-AKT1 pathway contributes to tumorigenesis and that the AKT1/mTOR is a novel therapeutic target for BRCA1-deficient cancers. Here, we report that phosphorylation of ribosomal prot...
متن کامل(ADP-Ribose) Polymerase as a Novel Therapeutic get in Cancer
Downloa cer chemotherapy exploits limitations in repairing DNA damage in order to kill proliferating nant cells. Recent evidence suggests that cancers within and across tissue types have specific defects A repair pathways, and that these defects may predispose for sensitivity and resistance to various s of cytotoxic agents. Poly (ADP-ribose) polymerase (PARP) and BRCA proteins are central to th...
متن کاملChromosomal instability syndromes are sensitive to poly ADP-ribose polymerase inhibitors.
Poly ADP-ribose polymerase inhibitors have been shown to target cells with homologous recombination DNA repair defects. We report that poly ADP-ribose polymerase inhibitors induces apoptosis in cells deficient in other key DNA repair components. Chromosomal instability disorders, Fanconi Anemia and Bloom's syndrome have dysfunctional DNA repair and an increased likelihood of leukemic transforma...
متن کاملGenome-wide analysis of gynecologic cancer: The Cancer Genome Atlas in ovarian and endometrial cancer.
Cancer typically develops due to genetic abnormalities, but a single gene abnormality cannot completely account for the onset of cancer. The Cancer Genome Atlas (CGA) project was conducted for the cross-sectional genome-wide analysis of numerous genetic abnormalities in various types of cancer. This approach has facilitated the identification of novel AT-rich interaction domain 1A gene mutation...
متن کاملSynergetic Effects of PARP Inhibitor AZD2281 and Cisplatin in Oral Squamous Cell Carcinoma in Vitro and in Vivo.
Cisplatin is a commonly used chemotherapeutic drug for treatment of oral carcinoma, and combinatorial effects are expected to exert greater therapeutic efficacy compared with monotherapy. Poly(ADP-ribosyl)ation is reported to be involved in a variety of cellular processes, such as DNA repair, cell death, telomere regulation, and genomic stability. Based on these properties, poly(ADP-ribose) pol...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Frontiers in bioscience
دوره 9 شماره
صفحات -
تاریخ انتشار 2017