Cixutumumab

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Cixutumumab
Monoclonal antibody
Type Whole antibody
Source Human
Target IGF-1 receptor
Clinical data
Routes of
administration
IV
ATC code
  • none
Identifiers
CAS Number
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C6500H10052N1724O2036S44
Molar mass 146.3 kg/mol
 ☒N☑Y (what is this?)  (verify)

Cixutumumab (IMC-A12) is a human monoclonal antibody for the treatment of solid tumors.[1][2]

This drug was developed by ImClone Systems, since acquired by Eli Lilly, using phage display technology from Dyax.

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.[3]

Research[edit]

Phase II clinical trials have been completed in patients with non-small cell lung cancer,[4][5] [6] metastatic rhabdomyosarcoma,[7] metastatic prostate cancer,[8] metastatic pancreatic cancer,[9] metastatic esophageal cancer,[10] bone cancer,[11][12] sarcoma,[13] solid tumors,[14] ocular melanoma,[15] hepatocellular carcinoma,[16][17], breast cancer[18] 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.[19]

References[edit]

  1. ^ Statement On A Nonproprietary Name Adopted By The Usan Council - Cixutumumab American Medical Association.
  2. ^ McKian, KP; Haluska, P (2009). "Cixutumumab". Expert Opinion on Investigational Drugs. 18 (7): 1025–33. doi:10.1517/13543780903055049. PMC 2939377. PMID 19548856.
  3. ^ [1] National Cancer InstituteTemplate:Http://www.cancer.gov/drugdictionary/?CdrID=561575
  4. ^ "BATTLE-FL: Front-Line Biomarker-Integrated Treatment Study in Non Small Cell Lung Cancer - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  5. ^ "Paclitaxel, Carboplatin, and Bevacizumab With or Without Cixutumumab in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  6. ^ "Carboplatin and Paclitaxel Combined With Cetuximab and/or IMC-A12 in Patients With Advanced Non-Small Cell Lung Cancer - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  7. ^ "Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  8. ^ "Bicalutamide and Goserelin or Leuprolide Acetate With or Without Cixutumumab in Treating Patients With Newly Diagnosed Metastatic Prostate Cancer - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  9. ^ "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 - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  10. ^ "Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  11. ^ "Temsirolimus and Cixutumumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Soft Tissue Sarcoma or Bone Sarcoma - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  12. ^ "A Five-Tier, Open-Label Study of IMC-A12 in Advanced Sarcoma - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  13. ^ "Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  14. ^ "Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  15. ^ "Cixutumumab in Treating Patients With Metastatic Melanoma of the Eye - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  16. ^ "A Study of IMC-A12 in Combination With Sorafenib in Patients With Advanced Cancer of the Liver - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  17. ^ "IMC-A12 in Treating Patients With Advanced Liver Cancer - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  18. ^ "A Study for Safety and Effectiveness of IMC-A12 by Itself or Combined With Antiestrogens to Treat Breast Cancer - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  19. ^ https://www.lilly.com/pipeline/index.html