Mechanisms of resistance to PARP inhibitors--three and counting.
نویسندگان
چکیده
Given the malleable nature of cancer cells, we should expect, and do see, the development of resistance to any new chemotherapeutic agent. Models that help us understand how this happens are a first step to better and more effective chemotherapeutics.
منابع مشابه
Understanding Resistance Mechanisms and Expanding the Therapeutic Utility of PARP Inhibitors
Poly-(ADP-ribose) polymerase (PARP) inhibitors act through synthetic lethality in cells with defects in homologous recombination (HR) DNA repair caused by molecular aberrations such as BRCA mutations, and is approved for treatment in ovarian cancer, with promising clinical activity against other HR defective tumors including breast and prostate cancers. Three PARP inhibitors have been FDA appro...
متن کامل“Back to a false normality”: new intriguing mechanisms of resistance to PARP inhibitors
Several evidences have shown that BRCA mutations increased tumor-cells sensitivity to PARP inhibitors by synthetic lethality leading to an accelerated development of several compounds targeting the PARP enzymes system as anticancer agents for clinical setting. Most of such compounds have been investigated in ovarian and breast cancer, showing promising efficacy in BRCA-mutated patients. Recentl...
متن کاملResistance to PARP-Inhibitors in Cancer Therapy
The pharmacological inhibitors of poly(ADP-ribose) polymerase (PARP) family of proteins have shown promising results in preclinical studies and clinical trials as a monotherapy or in combination therapy for some cancers. Thus, usage of PARP-inhibitors (PARPi) in cancer therapy is bound to increase with time, but resistance of cancer cells to PARPi is also beginning to be observed. Here we revie...
متن کاملMolecular pathways: how can BRCA-mutated tumors become resistant to PARP inhibitors?
PARP inhibition is synthetic lethal with defective DNA repair via homologous recombination. Phase I and II clinical trials show that PARP inhibitors are effective at well-tolerated doses and have antitumor activity for BRCA1- and BRCA2-associated cancers. However, not all patients respond equally well and tumors may eventually become resistant. Thus far, the only resistance mechanism that has b...
متن کاملReverse the Resistance to PARP Inhibitors
One of the DNA repair machineries is activated by Poly (ADP-ribose) Polymerase (PARP) enzyme. Particularly, this enzyme is involved in repair of damages to single-strand DNA, thus decreasing the chances of generating double-strand breaks in the genome. Therefore, the concept to block PARP enzymes by PARP inhibitor (PARPi) was appreciated in cancer treatment. PARPi has been designed and tested f...
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:
- Cancer discovery
دوره 3 1 شماره
صفحات -
تاریخ انتشار 2013