ArticlePediatric blood & cancer2011
Initial testing (stage 1) of the IGF-1 receptor inhibitor BMS-754807 by the pediatric preclinical testing program.
Article in Pediatric blood & cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed.
- Insulin-like Growth Factor 2 Gene Expression Molecularly Differentiates Pleuropulmonary Blastoma and Embryonal Rhabdomyosarcoma.Journal of pediatric hematology/oncology · 2015Trial
- 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
- Lessons learned from 20 years of preclinical testing in pediatric cancers.Pharmacology & therapeutics · 2024Review
- Article
- Preclinical Therapeutic Efficacy of RAF/MEK/ERK and IGF1R/AKT/mTOR Inhibition in Neuroblastoma.Cancers · 2024Article
- Optimizing preclinical pediatric low-grade glioma models for meaningful clinical translation.Neuro-oncology · 2023Article
- Costs and Causes of Oncology Drug Attrition With the Example of Insulin-Like Growth Factor-1 Receptor Inhibitors.JAMA network open · 2023Article
- Redundant Signaling as the Predominant Mechanism for Resistance to Antibodies Targeting the Type-I Insulin-Like Growth Factor Receptor in Cells Derived from Childhood Sarcoma.Molecular cancer therapeutics · 2023Article
- Metformin and an insulin/IGF-1 receptor inhibitor are synergistic in blocking growth of triple-negative breast cancer.Breast cancer research and treatment · 2021Article
- NLRR1 Is a Potential Therapeutic Target in Neuroblastoma and MYCN-Driven Malignant Cancers.Frontiers in oncology · 2021Article
- Effects of Heshouwuyin on gene expression of the insulin/IGF signalling pathway in rat testis and spermatogenic cells.Pharmaceutical biology · 2020Article
- Precision medicine in Ewing sarcoma: a translational point of view.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Review
- CYR61 triggers osteosarcoma metastatic spreading via an IGF1Rβ-dependent EMT-like process.BMC cancer · 2019Article
- Extracellular vesicle-mimetic nanovesicles transport LncRNA-H19 as competing endogenous RNA for the treatment of diabetic wounds.Drug delivery · 2018Article
- Protein Tyrosine Signaling and its Potential Therapeutic Implications in Carcinogenesis.Current pharmaceutical design · 2017Review
- A review of new agents evaluated against pediatric acute lymphoblastic leukemia by the Pediatric Preclinical Testing Program.Leukemia · 2016Review
- Present Advances and Future Perspectives of Molecular Targeted Therapy for Osteosarcoma.International journal of molecular sciences · 2016Review
- A dual-specific anti-IGF-1/IGF-2 human monoclonal antibody alone and in combination with temsirolimus for therapy of neuroblastoma.International journal of cancer · 2015Article
- Targeted therapies for advanced Ewing sarcoma family of tumors.Cancer treatment reviews · 2015Review
- Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
backgroundBMS-754807 is a small molecule ATP-competitive inhibitor of the type-1 insulin-like growth factor receptor currently in phase 1 clinical trials. PROCEDURES: BMS-754807 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro panel at concentrations ranging from 1.0 nM to 10 µM and was tested against the PPTP in vivo panels at a dose of 25 mg/kg administered orally BID for 6 days, repeated for 6 weeks.
resultsIn vitro BMS-754807 showed a median EC(50) value of 0.62 µM against the PPTP cell lines. The median EC(50) for the four Ewing sarcoma cell lines was less than that for the remaining PPTP cell lines (0.19 µM vs. 0.78 µM, P = 0.0470). In vivo BMS-754807 induced significant differences in EFS distribution compared to controls in 18 of 32 evaluable solid tumor xenografts (56%) tested, but in none of the ALL xenografts studied. Criteria for intermediate activity for the time to event activity measure (EFS T/C > 2) were met in 7 of 27 solid tumor xenografts evaluable for this measure. The best response was PD2 (progressive disease with growth delay), which was observed in 18 of 32 solid tumor xenografts. PD2 responses were most commonly observed in the rhabdomyosarcoma, neuroblastoma, osteosarcoma, Ewing sarcoma, and Wilms tumor panels.
conclusionsBMS-754807 activity in vitro is consistent with a specific IGF-1R effect that has half-maximal response in the 0.1 µM range and that is observed in a minority of the PPTP cell lines. In vivo intermediate activity was most commonly observed in the neuroblastoma and rhabdomyosarcoma panels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.