Alisertib (MLN8237), a selective Aurora-A kinase inhibitor, induces apoptosis in human tongue squamous cell carcinoma cell both in vitro and in vivo

Lin, Qi; Zhang, Yang

doi:10.1007/s13277-014-2782-3

Cited by 5 publications

(3 citation statements)

References 24 publications

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“…Similar to many previous studies on the molecular mechanisms of action of MLN8237 (11, 19, 22, 53–56), we demonstrated that apoptosis and cell cycle arrest in G 2 /M phase mediated the antitumor activity in pGBM both in vitro and in vivo . Despite the significantly prolonged animal survival time in IC-4687GBM, all the animals in the treatment group died of disease.…”

Section: Discussionsupporting

confidence: 90%

Concurrent Inhibition of Neurosphere and Monolayer Cells of Pediatric Glioblastoma by Aurora A Inhibitor MLN8237 Predicted Survival Extension in PDOX Models

Kogiso

Braun

et al. 2018

Clinical Cancer Research

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Pediatric glioblastoma multiforme (pGBM) is a highly aggressive tumor in need of novel therapies. Our objective was to demonstrate the therapeutic efficacy of MLN8237 (alisertib), an orally available selective inhibitor of Aurora A kinase (AURKA), and to evaluate which model system (monolayer or neurosphere) can predict therapeutic efficacy AURKA mRNA expressions were screened with qRT-PCR. antitumor effects were examined in three matching pairs of monolayer and neurosphere lines established from patient-derived orthotopic xenograft (PDOX) models of the untreated (IC-4687GBM), recurrent (IC-3752GBM), and terminal (IC-R0315GBM) tumors, and therapeutic efficacy through log rank analysis of survival times in two models (IC-4687GBM and IC-R0315GBM) following MLN8237 treatment (30 mg/kg/day, orally, 12 days). Drug concentrations and mechanism of action and resistance were also investigated. AURKA mRNA overexpression was detected in 14 pGBM tumors, 10 PDOX models, and 6 cultured pGBM lines as compared with 11 low-grade gliomas and normal brains. MLN8237 penetrated into pGBM xenografts in mouse brains. Significant extension of survival times were achieved in IC-4687GBM of which both neurosphere and monolayer were inhibited , but not in IC-R0315GBM of which only neurosphere cells responded (similar to IC-3752GBM). Apoptosis-mediated MLN8237 induced cell death, and the presence of AURKA-negative and CD133 cells appears to have contributed to therapy resistance. MLN8237 successfully targeted AURKA in a subset of pGBMs. Our data suggest that combination therapy should aim at AURKA-negative and/or CD133 pGBM cells to prevent tumor recurrence. .

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Section: Discussionsupporting

confidence: 90%

Concurrent Inhibition of Neurosphere and Monolayer Cells of Pediatric Glioblastoma by Aurora A Inhibitor MLN8237 Predicted Survival Extension in PDOX Models

Kogiso

Braun

et al. 2018

Clinical Cancer Research

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“…In preclinical data, Alisertib has been able to achieve robust anti-tumour efficacy that rationalized its further advancement to clinical trials (36)(37)(38)(39)(40)(41). Growth inhibition was achieved in a wide range of cell cultures, including cells originating from HTLV-1 infected adult T-cell leukemia (42), peripheral T-cell lymphomas (37), multiple myeloma (38), human tongue squamous cell carcinoma (39), malignant bladder cancer (40), and cervical cancer (36) cell lines. The latter were able to be completely cured in mouse xenograft models (36).…”

Section: Introductionmentioning

confidence: 99%

Critical risk-benefit assessment of the novel anti-cancer aurora a kinase inhibitor alisertib (MLN8237): A comprehensive review of the clinical data

Tayyar

Jubair

Fallaha

et al. 2017

Critical Reviews in Oncology/Hematology

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“…97-101 A number of xenografted-mouse studies have shown remarkable growth inhibition of solid tumours or haematologic malignancies when treated with alisertib alone or in combination with other anticancer agents. 22,[102][103][104][105][106]…”

Section: Mechanism Of Action and Binding Mode Of Alisertibmentioning

confidence: 99%

An update on the pharmacokinetics and pharmacodynamics of alisertib, a selective Aurora kinase A inhibitor

Durlacher

Chen

et al. 2016

Clin Exp Pharma Physio

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SUMMARYHuman Aurora kinases, including Aurora kinase A (AURKA), B (AURKB), and C (AURKC), play an essential role in mitotic events such as monitoring of the mitotic checkpoint, creation of bipolar mitotic spindle and alignment of centrosomes on it, also regulating centrosome separation, bioorientation of chromosomes and cytokinesis. AURKA and AURKB are key regulators of mitosis and centrosome via polymerizing microfilaments and controlling chromatid segregation. In particular, AURKA plays critical roles in the regulation of mitotic entry, centrosome function, bipolar spindle assembly, and chromosome segregation. AURKA has been found to be overexpressed in various solid and haematological cancers and has been linked with poor prognosis. Its important role in cancer initiation, growth, and metastasis has brought the focus to search for potent and selective AURKA inhibitors for cancer treatment. MLN8237, also known as alisertib, is one selective AURKA inhibitor that has shown remarkable anticancer effects in preclinical studies. Alisertib exhibits favourable pharmacokinetic properties. Alisertib has generally showed good partial response rates of 4-52% and good safety profiles in Phase I and II trials when it is solely administered as well as combined with cytotoxic chemotherapeutic drugs. Recently, the multicentre, randomized Phase III study of alisertib in patients with relapsed or refractory peripheral T-cell lymphoma has been discontinued due to unsatisfactory efficacy. The low risk of side effects, accessibility, and effectiveness of alisertib makes it a new promising anticancer therapy and further mechanistic and clinical studies are warranted.

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Alisertib (MLN8237), a selective Aurora-A kinase inhibitor, induces apoptosis in human tongue squamous cell carcinoma cell both in vitro and in vivo

Cited by 5 publications

References 24 publications

Concurrent Inhibition of Neurosphere and Monolayer Cells of Pediatric Glioblastoma by Aurora A Inhibitor MLN8237 Predicted Survival Extension in PDOX Models

Concurrent Inhibition of Neurosphere and Monolayer Cells of Pediatric Glioblastoma by Aurora A Inhibitor MLN8237 Predicted Survival Extension in PDOX Models

Critical risk-benefit assessment of the novel anti-cancer aurora a kinase inhibitor alisertib (MLN8237): A comprehensive review of the clinical data

An update on the pharmacokinetics and pharmacodynamics of alisertib, a selective Aurora kinase A inhibitor

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