Preclinical studies have shown that copper depletion therapy inhibits tumor growth, overcomes drug resistance such as Pt drugs, and potentiates antitumor immunotherapy via downregulation of programmed cell death ligand 1 (PD‐L1) expression.[76] However, some unavoidable side effects and systemic adverse reactions were found during the treatment, such as skin rash, optic neuritis, etc., which may be due to the nonselective removal of copper ions from the body by copper chelators.[77] Therefore, tumor‐targeted delivery of copper chelators is necessary for copper depletion therapy. This evidence concerns the gene CD274 and neoplasm.