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Multiple myeloma (MM)

IKAROS family zinc finger 1 (IKZF1; LYF1); IKZF3; cereblon (CRBN)

In vitro studies identified degradation of IKZF1 and IKZF3 as the anticancer mechanism of Revlimid lenalidomide. In MM cell lines, Revlimid upregulated expression of the CRBN ubiquitin ligase and promoted CRBN binding to the transcription factors IKZF1 and IKZF3, inducing their degradation. In MM cells, shRNA targeting CRBN or expression of a Revlimid-resistant CRBN mutant prevented Revlimid-induced degradation of IZKF1 and IZKF3. In Revlimid-sensitive MM cell lines, shRNA targeting IZKF1 or IZKF3 decreased cell survival compared with control shRNA. Next steps could include determining whether other IZKF1 and IZKF3 inhibitors cause teratogenicity.
Celgene Corp. markets Revlimid lenalidomide to treat hematologic cancers including MM.

SciBX 7(2); doi:10.1038/scibx.2014.53
Published online Jan. 16, 2014

Patent and licensing status unavailable for both studies

Kronke, J. et al. Science; published online Nov. 29, 2013;
Contact: Benjamin L. Ebert, Brigham and Women's Hospital, Boston, Mass.

Lu, G. et al. Science; published online Nov. 29, 2013;
Contact: William G. Kaelin Jr., Dana-Farber Cancer Institute, Boston, Mass.