Klin Onkol 2014; 27(5): 326-330. DOI: 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 eff ective 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 eff ects 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 eff ects. In addition, a correlation between CRBN gene expression and eff ectiveness of treatment in MM patients treated with IMiDs was confi rmed. These findings suggest that CRBN expression could possibly serve as a biomarker to predict response to IMiD in MM patients.
