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BEZ235

Novartis AG

Drug Names(s): NVP-BEZ235, dactolisib

Description: Novartis is currently developing a novel oral dual PI3K/mTOR inhibitor, BEZ235, which, in preclinical studies, showed high target specificity and demonstrated antiproliferative activity against tumor cell lines in animal models of cancer.

PI3Ks are key players in an intracellular signaling network, the so-called PI3K-PDK1-PKB pathway, which regulates cell proliferation, growth, survival, and apoptosis. A substantial number of epidemiological and experimental studies support an important role for PI3Ks in the biology of human cancer. The activation of PI3Ks and downstream effectors, including PKB (AKT) and mTOR, have been validated as an essential step for the initiation and maintenance of the tumorigenic phenotype.

Activation of the PI3K-PDK1-PKB pathway, via the loss of PTEN or the overexpression of some receptor tyrosine kinases (EGFR, HER-2), has been implicated in poor prognosis and survival in a number of tumor types, including breast, prostate, lung, glioblastoma, melanoma, and bladder; endometrial carcinoma; and lymphatic tumors. Inhibition of the PI3K pathway could result in increased apoptosis, decreased cell proliferation, decreased growth and decreased cell survival.


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