Metal-based molecules in the treatment of cancer: From bench to bedside

Cancer remains one of the leading causes of death in the world, with more than 9 million deaths in 2022, a number that continues to rise. This highlights the urgent need for the development of new drugs, with enhanced antitumor capabilities and fewer side effects. Metal-based drugs have been used in clinical practice since the late 1970s, beginning with the introduction of cisplatin. Later, two additional platinum-based molecules, carboplatin, and oxaliplatin, were introduced, and all three continue to be widely used in the treatment of various cancers. However, despite their significant anticancer activity, the undesirable side effects of these drugs have motivated the scientific community to explore other metal-based complexes with greater anticancer potential and fewer adverse effects. In this context, metals such as ruthenium, copper, gold, zinc, palladium, or iridium, present promising alternatives for the development of new anticancer agents. Unfortunately, although thousands of metal-based drugs have been synthesized and tested both in vitro and in animal models, only a few ruthenium-based drugs have entered clinical trials in recent years. Meanwhile, many other molecules with comparable or even greater anticancer potential have not advanced beyond the laboratory stage. In this review, we will revisit the mechanisms of action and anticancer activities of established platinum-based drugs and explore their use in recent clinical trials. Additionally, we will examine the development of potential new metal-based drugs that could one day contribute to cancer treatment worldwide.