cixutumumab

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| target = IGF-1 receptor

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Cixutumumab (IMC-A12) is a human monoclonal antibody for the treatment of solid tumors.{{cite web | url = http://www.ama-assn.org/ama1/pub/upload/mm/365/cixutumumab.pdf | title = Statement On A Nonproprietary Name Adopted – Cixutumumab | work = The USAN Council | publisher = American Medical Association }}{{cite journal | vauthors = McKian KP, Haluska P | title = Cixutumumab | journal = Expert Opinion on Investigational Drugs | volume = 18 | issue = 7 | pages = 1025–33 | date = July 2009 | pmid = 19548856 | pmc = 2939377 | doi = 10.1517/13543780903055049 }}

This drug was developed by ImClone Systems, since acquired by Eli Lilly, using phage display technology from Dyax.{{cn|date=February 2023}}

It is a fully human IgG1 monoclonal antibody directed against the human insulin-like growth factor-1 receptor (IGF-1R) with potential antineoplastic activity. Cixutumumab selectively binds to membrane-bound IGF-1R, thereby preventing the binding of the ligand IGF-1 and subsequent activation of PI3K/AKT signaling pathway. Downregulation of the PI3K/AKT survival pathway may result in the induction of cancer cell apoptosis and may decrease cancer cellular proliferation. IGF-1R, a receptor tyrosine kinase of the insulin receptor superfamily overexpressed by many cancer cell types, stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF-1R signaling has been implicated in tumorigenesis and metastasis.{{cite web | title = Cixutumumab | url = http://www.cancer.gov/drugdictionary/?CdrID=561575 | work = National Cancer Institute |date = 2011-02-02}}

Research

Phase II clinical trials have been completed in patients with non-small cell lung cancer,{{ClinicalTrialsGov|NCT01263782|BATTLE-FL: Front-Line Biomarker-Integrated Treatment Study in Non Small Cell Lung Cancer}}{{ClinicalTrialsGov|NCT00955305|Paclitaxel, Carboplatin, and Bevacizumab With or Without Cixutumumab in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer}}{{ClinicalTrialsGov|NCT00986674|Carboplatin and Paclitaxel Combined With Cetuximab and/or IMC-A12 in Patients With Advanced Non-Small Cell Lung Cancer}} metastatic rhabdomyosarcoma,{{ClinicalTrialsGov|NCT01055314|Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma}} metastatic prostate cancer,{{ClinicalTrialsGov|NCT01120236|Bicalutamide and Goserelin or Leuprolide Acetate With or Without Cixutumumab in Treating Patients With Newly Diagnosed Metastatic Prostate Cancer}} metastatic pancreatic cancer,{{ClinicalTrialsGov|NCT00617708|S0727 Gemcitabine Hydrochloride and Erlotinib Hydrochloride With or Without Monoclonal Antibody Therapy in Treating Patients With Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery}} metastatic esophageal cancer,{{ClinicalTrialsGov|NCT01142388|Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer}} bone cancer,{{ClinicalTrialsGov|NCT01016015|Temsirolimus and Cixutumumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Soft Tissue Sarcoma or Bone Sarcoma}} sarcoma,{{ClinicalTrialsGov|NCT01614795|Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma}} solid tumors,{{ClinicalTrialsGov|NCT00831844|Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors}} ocular melanoma,{{ClinicalTrialsGov|NCT01413191|Cixutumumab in Treating Patients With Metastatic Melanoma of the Eye}} hepatocellular carcinoma,{{ClinicalTrialsGov|NCT00906373|A Study of IMC-A12 in Combination With Sorafenib in Patients With Advanced Cancer of the Liver}}{{ClinicalTrialsGov|NCT00639509|IMC-A12 in Treating Patients With Advanced Liver Cancer}} breast cancer{{ClinicalTrialsGov|NCT00728949|A Study for Safety and Effectiveness of IMC-A12 by Itself or Combined With Antiestrogens to Treat Breast Cancer}} and other forms of cancer. Despite these extensive trials, more than 45 phase I and II clinical trials in total, phase III trials have never been undertaken and Eli Lilly has removed cixutumumab from their development pipeline.{{cite web | title = Clinical Development Pipeline | url = https://www.lilly.com/pipeline/index.html | archive-url = https://web.archive.org/web/20170113014056/https://www.lilly.com/pipeline/index.html | archive-date = 13 January 2017 | publisher = Eli Lilly and Company }}

References

Category:Monoclonal antibodies

Category:Experimental cancer drugs