The role of metals in cancer and the use of metal chelators as a potential treatment strategy.

Biometals such as iron, copper, zinc, manganese, cobalt, and selenium play crucial roles in cellular respiration, immunity, apoptosis, and signaling. However, their excessive accumulation can induce chronic inflammation, oxidative stress, and trigger carcinogenesis. Iron addiction stands out for its importance in tumor cell replication and survival. Cancer remains one of the leading causes of mortality worldwide. Given the limitations of conventional therapies, new approaches have been explored, namely the use of metal chelators, with the aim of selectively modulating metal homeostasis in tumor cells. Metal chelation represents a promising therapeutic approach in the treatment of cancer. Metal chelators such as DFO and DFX demonstrate antineoplastic activity, although limited by low selectivity and systemic toxicity. Thiosemicarbazones, particularly Triapine, have demonstrated anticancer and antimetastatic activity in preclinical models, with clinical trials currently underway to treat tumors. SK4 appears to be a promising alternative, with greater selectivity for tumor cells, inducing apoptosis, demonstrating superior efficacy and lower toxicity. Its efficacy in preclinical models and selective profile support the need for clinical validation, potentially integrating more targeted, safe, and effective oncological therapy. Thus, the aim of this manuscript is to analyze the role of metals in cancer and evaluate the therapeutic potential of metal chelators.