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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
- Source :
-
Cancer Cell . Mar2004, Vol. 5 Issue 3, p221. 10p. - Publication Year :
- 2004
-
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. [Copyright &y& Elsevier]
- Subjects :
- *CANCER
*PATHOLOGICAL physiology
*BLOOD diseases
*TUMORS
*CANCER cells
*THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 15356108
- Volume :
- 5
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Cancer Cell
- Publication Type :
- Academic Journal
- Accession number :
- 12639565
- Full Text :
- https://doi.org/10.1016/S1535-6108(04)00050-9