Cereblon – a New Target of Therapy in the Treatment of Multiple Myeloma

Česká verzia

Authors: M. Staňková ¹; L. Bešše ^1,2; L. Sedlaříková ^1,2; D. Vrábel ¹; R. Hájek ^1,2; S. Ševčíková ^1,2
Authors place of work: Babákova myelomová skupina, Ústav patologické fyziologie, LF MU, Brno ¹; Oddělení klinické hematologie, FN Brno ²
Published in the journal: Klin Onkol 2014; 27(5): 326-330
Category: Přehledy
doi: https://doi.org/10.14735/amko2014326

Summary

Treatment of multiple myeloma (MM), currently an incurable disease, aims to achieve complete remission. Immunomodulatory drugs (IMiDs), represented by thalidomide, are one class of very effective drugs. However, the mechanism of IMiDs action is not yet completely understood. Recent research suggests that cereblon (CRBN) plays an important role in mediating anti-tumor effects of IMiDs; therefore, our review focuses on this protein. CRBN is a substrate receptor of Cul4- E3 ubiquitin ligase complex, and thus recognizes proteins destined for degradation. Binding of CRBN and IMiDs inhibits function of the entire ubiquitin proteasome complex which partly explains their anti-tumor effects. In addition, a correlation between CRBN gene expression and effectiveness of treatment in MM patients treated with IMiDs was confirmed. These findings suggest that CRBN expression could possibly serve as a biomarker to predict response to IMiD in MM patients.

Key words:
cereblon – multiple myeloma – immunomodulatory drugs

This study was supported by grants IGA MZ CR NT14575 and NT12130.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Submitted:
12. 5. 2014

Accepted:
19. 5. 2014

Zdroje

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