Notably, the ectopic expression of RNF43 also downregulated the protein levels of the B‐RAF V600E mutant in UACC‐257 melanoma cells and the oncogenic B‐RAF deletion mutant in BxPC‐3 pancreatic cancer cells (Figure S1, Supporting Information).[25] Several studies have demonstrated that the application of proteolysis‐targeting chimeras (PROTACs) to trigger B‐RAF protein degradation has effective anti‐cancer activity.[26] Our data demonstrated that RNF43 targets wild‐type and mutant B‐RAF for degradation, and restoration of this E3 ligase may overcome B‐RAF inhibitor resistance. This evidence concerns the gene BRAF and familial pancreatic carcinoma.