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Multiple myeloma (MM)

Insulin-like growth factor-1 receptor (IGF1R; CD221); insulin-like growth factor-1 (IGF-1)

In vitro and mouse studies suggest antagonizing IGF1R could help prevent resistance to Velcade bortezomib in patients with MM. In bortezomib-resistant MM cells, secretion of IGF-1 and activation of IGF1R were greater than those in bortezomib-sensitive cells. In MM cells, small hairpin RNA against IGF1R increased sensitivity to bortezomib compared with scrambled shRNA. In MM cells and in mouse xenograft models of bortezomib-resistant MM, an IGF1R and insulin receptor inhibitor increased the antiproliferative and tumor-suppressive effects of bortezomib compared with bortezomib alone. Next steps could include testing the combination in additional models of MM.
At least 14 companies have IGF1R antagonists or antibodies in development stages ranging from preclinical to marketed to treat various indications.
Takeda Pharmaceutical Co. Ltd. and Johnson & Johnson market Velcade, a small molecule dipeptide boronic acid proteasome inhibitor, to treat MM and mantle cell lymphoma (MCL).

SciBX 5(38); doi:10.1038/scibx.2012.1001
Published online Sept. 27, 2012

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Kuhn, D.J. et al. Blood; published online
Aug. 29, 2012;
Contact: Robert Z. Orlowski, The University of Texas MD Anderson Cancer Center, Houston, Texas