CUL4B and Familial prostate cancer: For example, given that CRBN-based PROTACs are emerging as a promising approach for targeted therapy60, developments in this drug class must anticipate possible resistance via acquired alterations in CRBN and CUL4B. Indeed, in vitro CRISPR-Cas9-mediated loss-of-function screening in prostate cancer cells treated with a CRBN-based BRD4 degrader also predicted CRBN as the most likely candidate for drug resistance48.