Hepcidin Is a Valuable Therapeutic Target for Colorectal Cancer

Colorectal cancer (CRC) is one of the most frequent neoplasms and a major cause of cancer death worldwide. Despite recent advances in treatment approaches, the prognosis of advanced CRC remains poor, thus indicating the necessity of more effective treatments for CRC patients. CRC cells produce high levels of hepcidin, a peptide hormone that binds to the membrane-bound ferroportin and promotes its internalization and degradation, thus sequestering iron into the cancer cells with the downstream effect of enhancing tumor growth. Additionally, CRC cell-expressed hepcidin prolongs cell survival and, by targeting both CD8+ T cells and myeloid cells, restrains the induction of an efficient immune response against tumor antigens. The greatest expression of hepcidin is found in patients with metastatic CRC, and CRC patients with high hepcidin content have a worse survival rate than those with low hepcidin content. In the present article, we review the data supporting the prominent role of hepcidin in colon tumorigenesis and discuss how hepcidin inhibitors can help treat CRC patients in the metastatic setting with particular regard to the impact of hepcidin modulation on immunotherapeutic outcomes.