VHL and cancer: Thus far, a limited number of E3 ligases (e.g., CRBN, VHL,MDM2, IAP) are used for PROTAC development.36,42,43 However, drug resistance for PROTACs containingCRBN and VHL E3 ligase recruiters in tumors has already emerged.44 Besides, these E3 ligases are generally consideredto be ubiquitously expressed in humans, which show limited selectivityof PROTACs in cancer cells over normal cells.