2. Academic Validation
  3. 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

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.
Constantine S Mitsiades 1,  Nicholas S Mitsiades,  Ciaran J McMullan,  Vassiliki Poulaki,  Reshma Shringarpure,  Masaharu Akiyama,  Teru Hideshima,  Dharminder Chauhan,  Marie Joseph,  Towia A Libermann,  Carlos García-Echeverría,  Mark A Pearson,  Francesco Hofmann,  Kenneth C Anderson,  Andrew L Kung
Affiliations

Affiliation

  • 1 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. constantine_mitsiades@dfci.harvard.edu
PMID: 15050914 DOI: 10.1016/s1535-6108(04)00050-9
Abstract

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.

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