Thursday, September 27, 2012
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Multiple myeloma (MM)
Insulin-like growth factor-1 receptor (IGF1R;
growth factor-1 (IGF-1)
In vitro and mouse studies suggest antagonizing IGF1R could
help prevent resistance to Velcade
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.
Pharmaceutical Co. Ltd. and Johnson
& Johnson market Velcade, a small molecule dipeptide
boronic acid proteasome
inhibitor, to treat MM and mantle cell lymphoma (MCL).
Published online Sept. 27, 2012
Patent and licensing status
Kuhn, D.J. et al. Blood;
Aug. 29, 2012;
Contact: Robert Z. Orlowski, The University of Texas MD
Anderson Cancer Center, Houston, Texas
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