ArticleMolecular cancer therapeutics2011
Akt/mTOR counteract the antitumor activities of cixutumumab, an anti-insulin-like growth factor I receptor monoclonal antibody.
Article in Molecular cancer therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Trial
- Trial
- Trial
- Phase 2 trial of cixutumumab in children, adolescents, and young adults with refractory solid tumors: a report from the Children's Oncology Group.Pediatric blood & cancer · 2014Trial
- The Effects of Juglone on Cell Proliferation and Insulin-Like Growth Factor I Receptor/Phosphoinositide 3-Kinase/p85 (IGF-IR/PI3K/p85) Signaling Pathway in Pancreatic Cancer.Journal of clinical practice and research · 2025Article
- Review
- Mechanisms of drug resistance of pancreatic ductal adenocarcinoma at different levels.Bioscience reports · 2020Review
- Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy.Journal of hematology & oncology · 2020Review
- A Phase I Trial of the IGF-1R Antibody Ganitumab (AMG 479) in Combination with Everolimus (RAD001) and Panitumumab in Patients with Advanced Cancer.The oncologist · 2018Article
- mTOR co-targeting strategies for head and neck cancer therapy.Cancer metastasis reviews · 2017Review
- Update of IGF-1 receptor inhibitor (ganitumab, dalotuzumab, cixutumumab, teprotumumab and figitumumab) effects on cancer therapy.Oncotarget · 2017Review
- Article
- Type I insulin-like growth factor receptor signaling in hematological malignancies.Oncotarget · 2017Review
- Targeted therapy for soft tissue sarcomas in adolescents and young adults.Adolescent health, medicine and therapeutics · 2017Review
- Essential role of insulin-like growth factor 2 in resistance to histone deacetylase inhibitors.Oncogene · 2016Article
- Evasion of anti-growth signaling: A key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds.Seminars in cancer biology · 2015Review
- Targeting the insulin-like growth factor receptor and Src signaling network for the treatment of non-small cell lung cancer.Molecular cancer · 2015Article
- Safety, tolerability, and pharmacokinetics of single and multiple doses of intravenous cixutumumab (IMC-A12), an inhibitor of the insulin-like growth factor-I receptor, administered weekly or every 2 weeks in patients with advanced solid tumors.Investigational new drugs · 2015Article
- Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3.Journal of ovarian research · 2014Article
- Combination of anti-HER3 antibody MM-121/SAR256212 and cetuximab inhibits tumor growth in preclinical models of head and neck squamous cell carcinoma.Molecular cancer therapeutics · 2014Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Recent reports have shown limited anticancer therapeutic efficacy of insulin-like growth factor receptor (IGF-1R)-targeted monoclonal antibodies (mAb), but the resistance mechanisms have not been completely identified. Because cooperation between epidermal growth factor receptor (EGFR) and IGF-IR could cause resistance to inhibitors of individual receptor tyrosine kinases, we investigated the involvement of EGFR signaling in resistance to IGF-1R mAb and the underlying mechanisms of action. Most head and neck squamous cell carcinoma (HNSCC) tissues had coexpression of total and phosphorylated IGF-1R and EGFR at high levels compared with paired adjacent normal tissues. Treatment with cixutumumab (IMC-A12), a fully humanized IgG1 mAb, induced activation of Akt and mTOR, resulting in de novo synthesis of EGFR, Akt1, and survivin proteins and activation of the EGFR pathway in cixutumumab-resistant HNSCC and non-small cell lung cancer (NSCLC) cells. Targeting mTOR and EGFR pathways by treatment with rapamycin and cetuximab (an anti-EGFR mAb), respectively, prevented cixutumumab-induced expression of EGFR, Akt, and survivin and induced synergistic antitumor effects in vitro and in vivo. These data show that resistance to IGF-1R inhibition by mAbs is associated with Akt/mTOR-directed enhanced synthesis of EGFR, Akt1, and survivin. Our findings suggest that Akt/mTOR might be effective targets to overcome the resistance to IGF-1R mAbs in HNSCC and NSCLC.
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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.