CRBN and plasma cell myeloma: Variation of E3 expression is also likely to be a key factor in acquired resistance to PROTACs: A genome-wide CRISPR-Cas9 screen in myeloma cells treated with PROTACs for various targets showed that it was loss of function of CRBN/VHL, rather than ‘work-around’ mechanisms for the loss of the respective oncoprotein target, which underpinned resistance to degradation55.