Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumors

Cancer Cell. 2004 Mar;5(3):221-30. doi: 10.1016/s1535-6108(04)00050-9.


Insulin-like growth factors and their receptor (IGF-1R) have been implicated in cancer pathophysiology. We demonstrate that IGF-1R is universally expressed in various hematologic (multiple myeloma, lymphoma, leukemia) and solid tumor (breast, prostate, lung, colon, thyroid, renal, adrenal cancer, retinoblastoma, and sarcoma) cells. Specific IGF-1R inhibition with neutralizing antibody, antagonistic peptide, or the selective kinase inhibitor NVP-ADW742 has in vitro activity against diverse tumor cell types (particularly multiple myeloma), even those resistant to conventional therapies, and triggers pleiotropic antiproliferative/proapoptotic molecular sequelae, delineated by global transcriptional and proteomic profiling. NVP-ADW742 monotherapy or its combination with cytotoxic chemotherapy had significant antitumor activity in an orthotopic xenograft MM model, providing in vivo proof of principle for therapeutic use of selective IGF-1R inhibitors in cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents
  • Bone Marrow / metabolism
  • Enzyme Inhibitors / pharmacology
  • Flow Cytometry
  • Gene Expression Profiling
  • Hematologic Neoplasms / drug therapy
  • Hematologic Neoplasms / metabolism*
  • Humans
  • Insulin-Like Growth Factor I / metabolism*
  • Multiple Myeloma
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Pyrimidines / pharmacology
  • Pyrroles / pharmacology
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Receptor, IGF Type 1 / metabolism*
  • Transplantation, Heterologous / pathology
  • Vascular Endothelial Growth Factor A / metabolism


  • ADW 742
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Pyrimidines
  • Pyrroles
  • Vascular Endothelial Growth Factor A
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1