ATR kinase inhibitors NVP-BEZ235 and AZD6738 effectively penetrate the brain after systemic administration
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چکیده
منابع مشابه
NVP-BEZ235 and NVP-BGT226, dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors, enhance tumor and endothelial cell radiosensitivity
BACKGROUND The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in tumor cells and promotes tumor cell survival after radiation-induced DNA damage. Because the pathway may not be completely inhibited after blockade of PI3K itself, due to feedback through mammalian target of rapamycin (mTOR), more effective inhibition might be expected by targeting both PI3K and mTOR inhibition. M...
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Osteosarcoma(OS) remains a major health concern in childhood and adolescence, although cisplatin is one of the gold standard chemotherapeutic drugs in the treatment of OS, chemoresistant to cisplatin is common. Phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin inhibitor (mTOR) pathway and autophagy regulates chemosensitivity incancer cells. In this study, we hypothesized that N...
متن کاملPI3K and mTOR inhibitor, NVP-BEZ235, is more toxic than X-rays in prostate cancer cells
Background: Radiotherapy and adjuvant androgen deprivation therapy have historically been the first treatment choices for prostate cancer but treatment resistance often limits the capacity to effectively manage the disease. Therefore, alternative therapeutic approaches are needed. Here, the efficacies of radiotherapy and targeting the pro-survival cell signaling components epidermal growth fact...
متن کاملPhosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235.
Small molecule inhibitors of HER2 are clinically active in women with advanced HER2-positive breast cancer who have progressed on trastuzumab treatment. However, the effectiveness of this class of agents is limited by either primary resistance or acquired resistance. Using an unbiased genetic approach, we performed a genome wide loss-of-function short hairpin RNA screen to identify novel modula...
متن کاملThe orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of cisplatin to resolve ATM-deficient non-small cell lung cancer in vivo.
ATR and ATM are DNA damage signaling kinases that phosphorylate several thousand substrates. ATR kinase activity is increased at damaged replication forks and resected DNA double-strand breaks (DSBs). ATM kinase activity is increased at DSBs. ATM has been widely studied since ataxia telangiectasia individuals who express no ATM protein are the most radiosensitive patients identified. Since ATM ...
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ژورنال
عنوان ژورنال: Radiation Oncology
سال: 2018
ISSN: 1748-717X
DOI: 10.1186/s13014-018-1020-3