How Thalidomide Works Against Cancer

The surprising ability of thalidomide and its analogs to treat various hematologic malignancies is through the loss of two transcription factors. [Also see Reports by Krönke et al. and Lu et al. ] The 55-year history of the drug thalidomide is Shakespearean in scope, awash in unintended consequences, tragedy, resilience, driven characters, and redemption. Indeed, the most notorious pharmaceutical of modern times comes replete with images of devastating birth defects still firmly embedded in the public consciousness. Less well known has been the resurgence in its use as a therapy to treat hematologic malignancy. On pages 305 and 301 of this issue, Lu et al. ( 1 ) and Krönke et al. ( 2 ), respectively, report that thalidomide and derivative compounds have a toxic effect on multiple myeloma by causing the degradation of two transcription factors, Ikaros and Aiolos. This loss halts myeloma growth while simultaneously altering immune cell function.