Title of article :
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
Author/Authors :
Mitsiades، نويسنده , , Constantine S and Mitsiades، نويسنده , , Nicholas S and McMullan، نويسنده , , Ciaran J and Poulaki، نويسنده , , Vassiliki and Shringarpure، نويسنده , , Reshma and Akiyama، نويسنده , , Masaharu and Hideshima، نويسنده , , Teru and Chauhan، نويسنده , , Dharminder and Joseph، نويسنده , , Marie and Libermann، نويسنده , , Towia A and Garc??a-Echeverr??a، نويسنده , , Carlos and Pearson، نويسنده , , Mark A and Hofmann، نويسنده , , Francesco and Anderson، نويسنده , , Kenneth C and Kung، نويسنده , , Andrew L، نويسنده ,
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.
