Resistance to immunomodulatory drugs in multiple myeloma: the cereblon pathway and beyond
Phaik Ju Teoh,
Mun Yee Koh,
Constantine Mitsiades,
Sarah Gooding,
Wee Joo Chng
Affiliations
Phaik Ju Teoh
Cancer 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
Mun Yee Koh
Cancer Science Institute of Singapore, National University of Singapore, 117599
Constantine Mitsiades
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
Sarah Gooding
Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK; Oxford Centre for Translational Myeloma Research, University of Oxford, Oxford, OX1 2JD, UK; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS
Wee Joo Chng
Cancer 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 Haematology, Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, 119228
Acquired resistance to immunomodulatory drugs (IMiDs) remains a significant unmet need in the treatment landscape of multiple myeloma (MM). 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.
