ArticlePediatric blood & cancer2010
Initial testing of the aurora kinase A inhibitor MLN8237 by the Pediatric Preclinical Testing Program (PPTP).
Article in Pediatric blood & cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
139 citing papers in PubMed.
- Population Pharmacokinetics and Exposure-Safety Relationships of Alisertib in Children and Adolescents With Advanced Malignancies.Journal of clinical pharmacology · 2022Trial
- A Phase II Study of Alisertib in Children with Recurrent/Refractory Solid Tumors or Leukemia: Children's Oncology Group Phase I and Pilot Consortium (ADVL0921).Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- Phase II Trial of Alisertib in Combination with Irinotecan and Temozolomide for Patients with Relapsed or Refractory Neuroblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Trial
- Phase II study of alisertib, a selective Aurora A kinase inhibitor, in relapsed and refractory aggressive B- and T-cell non-Hodgkin lymphomas.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2014Trial
- Targeted and molecular therapies in Ewing sarcoma: a comprehensive review of preclinical and clinical advances.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Article
- Image-guided targeting of mitochondrial metabolism sensitizes pediatric malignant rhabdoid tumors to low-dose radiotherapy.Science advances · 2025Article
- Rhabdoid Tumor of the Kidney and Soft Tissues: Results from National Wilms Tumor Study-5 and Children's Oncology Group Study AREN0321.Pediatric blood & cancer · 2025Article
- MYCN as an oncogene in pediatric brain tumors.Frontiers in oncology · 2025Review
- Lessons learned from 20 years of preclinical testing in pediatric cancers.Pharmacology & therapeutics · 2024Review
- Aurora Kinase A inhibition enhances DNA damage and tumor cell death withEJNMMI research · 2024Article
- Centrosomes and associated proteins in pathogenesis and treatment of breast cancer.Frontiers in oncology · 2024Review
- Review
- Review
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- Article
- Current and Emerging Therapeutic Approaches for Extracranial Malignant Rhabdoid Tumors.Cancer management and research · 2022Review
- Advancing therapy for osteosarcoma.Nature reviews. Clinical oncology · 2021Review
- Aurora Kinase A proximity map reveals centriolar satellites as regulators of its ciliary function.EMBO reports · 2021Article
- An analysis of the diagnosis, clinical characteristics, treatment, and survival outcomes of 36 extracranial malignant rhabdoid tumor patients.Translational pediatrics · 2021Article
79 more citing papers are in PubMed but not listed here.
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12 authors.
Funding
Abstract
backgroundMLN8237 is a small molecule inhibitor of Aurora Kinase A (AURKA) that is currently in early phase clinical testing. AURKA plays a pivotal role in centrosome maturation and spindle formation during mitosis. PROCEDURES: MLN8237 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro panel at concentrations ranging from 1.0 nM to 10 microM and was tested against the PPTP in vivo panels at a dose of 20 mg/kg administered orally twice daily x 5 days. Treatment duration was 6 weeks for solid tumor xenografts and 3 weeks for ALL xenografts.
resultsMLN8237 had a median IC(50) of 61 nM against the PPTP in vitro panel. The ALL cell lines were more sensitive and the rhabdomyosarcoma cell lines less sensitive than the remaining PPTP cell lines. In vivo, MLN8237 induced significant differences in event-free survival (EFS) distributions compared to controls in 32/40 (80%) solid tumor models and all (6/6) ALL models. Maintained complete responses (CRs) were observed in 3 of 7 neuroblastoma xenografts, and all 6 evaluable ALL xenografts achieved CR (n = 4) or maintained CR (n = 2) status. Maintained CRs were observed among single xenografts in other panels, including the Wilms tumor, rhabdoid tumor, rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, and medulloblastoma.
conclusionsThe in vivo activity observed against the neuroblastoma panel far exceeds that observed for standard agents evaluated against the panel by the PPTP. High levels of in vivo activity were also observed against the ALL xenograft panel. These data support expedited clinical development of MLN8237 in childhood cancer.
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