PARP inhibitors and more.
نویسندگان
چکیده
Polyadenosine diphosphate (ADP) ribose polymerase (PARP) lends a panoramic view to the inner mystery of protection of integrity of deoxyribonucleic acid (DNA) in a cell genome. They are a balancing part of an even more dynamic equilibrium of normalcy against daily assaults. PARP finds its companion candidates in other tumor suppressors, with the most prominent and glaring one being breast cancer (BRCA) 1 and 2. The strength of both is split by PARP inhibitors, inculcating the synthetic lethality of tumor cell, which is now in the market for ovarian cancer treatment. There are many reasons for the resistance of such inhibitors, which are now becoming clinically important. These are seen along with other damage repair approaches.
منابع مشابه
Rationale for poly(ADP-ribose) polymerase (PARP) inhibitors in combination therapy with camptothecins or temozolomide based on PARP trapping versus catalytic inhibition.
We recently showed that poly(ADP-ribose) polymerase (PARP) inhibitors exert their cytotoxicity primarily by trapping PARP-DNA complexes in addition to their NAD(+)-competitive catalytic inhibitory mechanism. PARP trapping is drug-specific, with olaparib exhibiting a greater ability than veliparib, whereas both compounds are potent catalytic PARP inhibitors. Here, we evaluated the combination of...
متن کاملPoly-(ADP-ribose)-polymerase inhibitors as radiosensitizers: a systematic review of pre-clinical and clinical human studies
BACKGROUND Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors are becoming important actors of anti-neoplasic agents landscape, with recent but narrow FDA's approvals for ovarian BRCA mutated cancers and prostatic cancer. Nevertheless, PARP inhibitors are also promising drugs for combined treatments particularly with radiotherapy. More than seven PARP inhibitors have been currently developed. Centr...
متن کاملTrapping of PARP1 and PARP2 by Clinical PARP Inhibitors.
Small-molecule inhibitors of PARP are thought to mediate their antitumor effects as catalytic inhibitors that block repair of DNA single-strand breaks (SSB). However, the mechanism of action of PARP inhibitors with regard to their effects in cancer cells is not fully understood. In this study, we show that PARP inhibitors trap the PARP1 and PARP2 enzymes at damaged DNA. Trapped PARP-DNA complex...
متن کاملPARP Inhibitors for Recurrent Ovarian Carcinoma: Current Treatment Options and Future Perspectives.
More than simply a promising management option, PARP inhibitors can be regarded as a milestone in the development of personalised treatment of recurrent ovarian carcinoma. Their mechanism of action, known as "synthetic lethality", is dependent on functional differences of the DNA repair mechanisms of healthy cells and tumour cells; cells that repair DNA damage less efficiently are particularly ...
متن کاملStereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib.
Anti-PARP drugs were initially developed as catalytic inhibitors to block the repair of DNA single-strand breaks. We recently reported that several PARP inhibitors have an additional cytotoxic mechanism by trapping PARP-DNA complexes, and that both olaparib and niraparib act as PARP poisons at pharmacologic concentrations. Therefore, we have proposed that PARP inhibitors should be evaluated bas...
متن کاملINVITED COMMENTARY Biomarkers of PARP inhibitor sensitivity
The PARP inhibitors represent one of the most exciting recent developments in cancer therapy. Substantial efficacy has been shown with PARP inhibitors in the treatment of hereditary BRCA1/2 related Breast and Ovarian cancer as single agents [1–3] and in combination with temozolomide [4]. Similarly, encouraging activity has been shown in sporadic ovarian cancer with a PARP inhibitor as a single ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of the Turkish German Gynecological Association
دوره 16 2 شماره
صفحات -
تاریخ انتشار 2015