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Updated: Jun 7, 2025

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
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Published on: May 15, 2019

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Resistance to immunomodulatory drugs in multiple myeloma: the cereblon pathway and beyond

Phaik Ju Teoh1, Mun Yee Koh2, Constantine Mitsiades3

  • 1Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore; Division of Molecular and Cellular Oncology (MCO), Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, 02142. mdctpju@nus.edu.sg.

Haematologica
|November 21, 2024
PubMed

Acquired resistance to immunomodulatory drugs (IMiD) remains a significant unmet need in the treatment landscape of multiple myeloma (MM). The cereblon (CRBN) pathway-dependent mechanisms are known to be vital contributors to IMiD resistance; however, they may account for only a small proportion. Recent research has unveiled additional mechanisms of acquired IMiD resistance that are independent of the CRBN pathway. In this review, we provide a comprehensive overview of the existing work on IMiD resistance in MM, focusing specifically on the emerging evidence of CRBN pathway-independent mechanisms. Finally, we discuss the plausible actionable strategies and outlook for IMiD-based therapies moving forward.

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