Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against T-cell acute lymphoblastic leukemia.

@article{Chiarini2010ActivityOT,
  title={Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against T-cell acute lymphoblastic leukemia.},
  author={Francesca Chiarini and Cecilia Grimaldi and Francesca Ricci and Pier Luigi Tazzari and Camilla Evangelisti and Andrea Ognibene and Michela Battistelli and Elisabetta Falcieri and Fraia Melchionda and Andrea Pession and Pasquale Pagliaro and James Andrew McCubrey and Alberto Maria Martelli},
  journal={Cancer research},
  year={2010},
  volume={70 20},
  pages={
          8097-107
        }
}
Recent findings have highlighted that constitutively active phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling is a common feature of T-cell acute lymphoblastic leukemia (T-ALL), where it upregulates cell proliferation, survival, and drug resistance. These observations lend compelling weight to the application of PI3K/Akt/mTOR inhibitors in the therapy of T-ALL. Here, we have analyzed the therapeutic potential of the novel dual PI3K/mTOR inhibitor NVP-BEZ235… 
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Effects of NVP-BEZ235, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, on HTLV-1-infected T-cell lines.
TLDR
The results of the current study provide preclinical rationale for phase I clinical studies to examine the effects of NVP-BEZ235 in patients with ATL and highlight the efficacious dual inhibition of PI3K, and mTOR following N VP-BEz235 treatment.
The dual kinase inhibitor NVP-BEZ235 in combination with cytotoxic drugs exerts anti-proliferative activity towards acute lymphoblastic leukemia cells.
TLDR
NVP-BEZ235 displays pronounced antiproliferative effects in ALL cells and might therefore be a useful drug in the treatment of ALL and synergistically enhanced the cytotoxicity compared to single-drug treatment, even in glucocorticoid-resistant cells.
NVP-BEZ235 and NVP-BGT226, dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors, enhance tumor and endothelial cell radiosensitivity
TLDR
It is demonstrated that PI3K/mTOR inhibitors can enhance radiation-induced killing in tumor and endothelial cells and may be of benefit when combined with radiotherapy.
The dual PI3K and mTOR inhibitor NVP-BEZ235 exhibits anti-proliferative activity and overcomes bortezomib resistance in mantle cell lymphoma cells.
Two hits are better than one: targeting both phosphatidylinositol 3-kinase and mammalian target of rapamycin as a therapeutic strategy for acute leukemia treatment
TLDR
The evidence documenting that dual PI3K/mTOR inhibitors may represent a promising option for future targeted therapies of acute leukemia patients is reviewed.
AMP-dependent kinase/mammalian target of rapamycin complex 1 signaling in T-cell acute lymphoblastic leukemia: therapeutic implications
TLDR
In conclusion, metformin displayed a remarkable anti-leukemic activity, which emphasizes future development of LKB1/AMPK activators as clinical candidates for therapy in T-ALL.
Chemical Therapeutics Dual PI 3 K / AKT / mTOR Inhibitor BEZ 235 Synergistically Enhances the Activity of JAK 2 Inhibitor against Cultured and Primary Human Myeloproliferative Neoplasm Cells
TLDR
Treatment with the dual phosphoinositide-3-kinase (PI3K)/AKT and mTOR inhibitor BEZ235 attenuated PI3K/AKT/mTOR signaling, as well as induced cell-cycle growth arrest and apoptosis of the cultured human JAK2-V617F-expressing HEL92.1.7.7 cells.
The Dual PI 3 K / mTOR Inhibitor NVP-BEZ 235 Is a Potent Inhibitor of ATM-and DNA-PKCs-Mediated DNA Damage Responses 1 , 2
TLDR
It is shown that NVP-BEZ235 also potently inhibits ATM and DNA-PKcs, the two major kinases responding to ionizing radiation (IR)–induced DNA double-strand breaks (DSBs), which has important implications for the informed and rational design of clinical trials involving this drug and also reveals the potential utility of N VP-BEz235 as an effective radiosensitizer for GBMs in the clinic.
The dual PI3K/mTOR inhibitor NVP-BEZ235 is a potent inhibitor of ATM- and DNA-PKCs-mediated DNA damage responses.
TLDR
It is shown that NVP-BEZ235 is a potent and novel inhibitor of ATM and DNA-PKcs, the two major kinases responding to ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) and significantly impairs DSB repair in a mouse tumor model thereby validating the efficacy of this drug as a DNA repair inhibitor in vivo.
Dual PI3K/mTOR inhibition is required to effectively impair microenvironment survival signals in mantle cell lymphoma
TLDR
NVP-BEZ235 was the only drug able to block IL4 and IL6/STAT3 signaling which compromise the therapeutic effect of chemotherapy in MCL and support the use of the dual PI3K/mTOR inhibitor NVP- BEZ235 as a promising approach to interfere with the microenvironment-related processes in M CL.
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