2007
DOI: 10.1158/1078-0432.ccr-06-2979
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Abstract: Purpose: In the current study, we examined the in vivo effects of AZD1152, a novel and specific inhibitor of Aurora kinase activity (with selectivity for Aurora B). Experimental Design: The pharmacodynamic effects and efficacy of AZD1152 were determined in a panel of human tumor xenograft models. AZD1152 was dosed via several parenteral (s.c. osmotic mini-pump, i.p., and i.v.) routes. Results: AZD1152 potently inhibited the growth of human colon, lung, and hematologic tumor xenografts (mean tumor growth inhibi… Show more

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Cited by 324 publications
(299 citation statements)
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“…Although competitive inhibition is observed in PC3 cells too, synergism was also observed in PC3 cells, as they are highly susceptible to any decrease in the expression levels of either AURKB or EGFR. Similar results are reported earlier by Wilkinson et al 13 in which treatment of cells with AURKB inhibitor, AZD1152, led to failure of cell division, causing accumulation of cells in 4N followed by induction of apoptotic cell death. EGFR-driven signaling not only controls cancer cell proliferation, but also is responsible for tumor progression, including apoptosis, invasion, and angiogenesis.…”
Section: Aurkb-egfr Knockdown Shows Enhanced Therapeutic Efficacysupporting
confidence: 91%
“…Although competitive inhibition is observed in PC3 cells too, synergism was also observed in PC3 cells, as they are highly susceptible to any decrease in the expression levels of either AURKB or EGFR. Similar results are reported earlier by Wilkinson et al 13 in which treatment of cells with AURKB inhibitor, AZD1152, led to failure of cell division, causing accumulation of cells in 4N followed by induction of apoptotic cell death. EGFR-driven signaling not only controls cancer cell proliferation, but also is responsible for tumor progression, including apoptosis, invasion, and angiogenesis.…”
Section: Aurkb-egfr Knockdown Shows Enhanced Therapeutic Efficacysupporting
confidence: 91%
“…Under these conditions, the signal for the active form of AurB at the spindle midzone as detected with an anti-pT232 AurB antibody was not compromised (supplementary Fig S1C online). As expected, active AurB was not detectable anymore in cells incubated with the AurB inhibitor AZD1152 (AZD) [14] (supplementary Fig S1C online). We conclude that MLN inhibits AurA at 250 nM without compromising AurB activity and we performed all the subsequent experiments using this inhibitor concentration.…”
Section: Resultssupporting
confidence: 71%
“…The Aurora kinases represent one such class of molecular targets that are essential for progression through mitosis, and small molecule inhibitors of these kinases possess broad antitumor efficacy that has not yet been shown to discriminate on a cancer genetic basis. 7,11 Although it has been demonstrated that cancer cells deficient in p53 show accelerated polyploidization when treated with VX-680, 23 this does not appear to represent genetic susceptibility per se as cells harboring wild-type p53 are also subject to polyploidization-mediated cell death, though perhaps with delayed kinetics. Our data provide genetic evidence to indicate that the Aurora kinase inhibitor, AZD1152, which is currently undergoing clinical evaluation and potentially of another clinical compound, VX-680, may be relatively ineffective in tumor cells that overexpress MDR1 or BCRP.…”
Section: Discussionmentioning
confidence: 99%
“…Transient myelosuppression was observed secondary to inhibition of proliferation of the bone marrow, though this effect was fully reversible following cessation of AZD1152 treatment. 11 A major obstacle faced during cancer chemotherapy is the development of cross-resistance of tumors to cytotoxic agents, even to drugs to which the tumor cells were never exposed. This phenotype, known as multidrug resistance (MDR), is frequently observed following treatment with anticancer drugs.…”
Section: Introductionmentioning
confidence: 99%