Copper compounds as anti-colorectal cancer agents

Introduction: One-third of cancer related deaths are due to the behavioral risk factors and dietary. The trace element copper (Cu) is vital for numerous biological processes. Recently, copper-related mechanisms have been suggested as preventive and therapeutic targets in cancer. Therefore, the aim of this review was to verify the therapeutic benefits of copper in colorectal cancer (CRC) treatment.Description: We searched relevant articles between 2000-2020, in electronic databases MEDLINE, COCHRANE and EMBASE. Only relevant English articles were included. It has reported that CRC patients with drug-resistant tumors have remarkably more serum copper respect to the drug-sensitive ones. Cu concentration has been proven extremely increased in cancer tissues for promoting cancer development. Angiogenesis and the neovascularization are the main processes in tumor growth and metastasis that require Cu as an essential co-factor. Proliferation and migration of endothelial cells are stimulated by this element. Some proangiogenic mediators can be decreased using the anti-copper drugs. Moreover, the role of Cu in BRAF signaling modulation is particularly relevant in CRC. Most of the BRAFV600E mutant CRC patients have respectively extremely more serum copper than healthy and do not respond to BRAF inhibition monotherapy. Therefore, as an adjuvant therapy, copper chelation therapy can possibly be proposed in BRAFV600E CRC patients. In addition, more sensitivity to proteasome inhibition has been reported in cancer cells respect to the normal cells. Since proteasome inhibition has lower toxicity, certain classes of organic compounds can be used to target copper in cancer cells that result in greatly effective and selective cancer killing that avoids toxicity.Discussion and conclusion: Taken together, optimize and develop more potent and specific anticancer copper ligands may represent a promising therapeutic strategy in colorectal cancer therapy.