Metallodrugs: an approach against invasion and metastasis in cancer treatment

• Published in: FEBS open bio Vol. 12; no. 5; pp. 880 - 899
• Main Authors: González‐Ballesteros, Mauricio M., Mejia, Carmen, Ruiz‐Azuara, Lena
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.05.2022; John Wiley and Sons Inc; Wiley
• Subjects: Aluminum; Angiogenesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic drugs; Antitumor agents; Apoptosis; bioactive properties; Biological activity; Blood vessels; Cancer; Cancer therapies; cancer therapy; Cell death; Cell proliferation; Chemotherapy; Cisplatin; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; death; DNA; Drug development; Epidermal growth factor; Extracellular matrix; Guanine; Humans; Hyaluronic acid; Inorganic compounds; invasion; Invasiveness; Ions; Kinases; ligands; mechanism of action; Medical prognosis; Metal ions; metallodrugs; Metals - chemistry; Metals - pharmacology; Metastases; Metastasis; Minimum inhibitory concentration; mortality; neoplasm progression; Neoplasms - drug therapy; Nonsteroidal anti-inflammatory drugs; Proteins; Redox properties; Review; stereochemistry; transition metals; Tumor necrosis factor-TNF; Vascular endothelial growth factor; cancer; metallodrugs; invasion; metastasis; transition metals
• ISSN: 2211-5463; 2211-5463
• DOI: 10.1002/2211-5463.13381

Cancer is a heterogeneous and multifactorial disease that causes high mortality throughout the world; therefore, finding the most effective therapies is a major research challenge. Currently, most anticancer drugs present a limited number of well‐established targets, such as cell proliferation or death; however, it is important to consider that the worse progression of cancer toward pathological stages implies invasion and metastasis processes. Medicinal Inorganic Chemistry (MIC) is a young area that deals with the design, synthesis, characterization, preclinical evaluation, and mechanism of action of new inorganic compounds, called metallodrugs. The properties of metallic ions allow enriching of strategies for the design of new drugs, enabling the adjustment of physicochemical and stereochemical properties. Metallodrugs can adopt geometries, such as tetrahedral, octahedral, square planar, and square planar pyramid, which adjusts their arrangement and facilitates binding with a wide variety of targets. The redox properties of some metal ions can be modulated by the presence of the bound ligands to adjust their interaction, thereby opening a range of mechanisms of action. In this regard, the mechanisms of action that trigger the biological activity of metallodrugs have been generally identified by: (a) coordination of the metal to biomolecules (for instance, cisplatin binds to the N7 in DNA guanine, as Pt‐N via coordination of the inhibition of enzymes); (b) redox‐active; and (c) ROS production. For this reason, a series of metallodrugs can interact with several specific targets in the anti‐invasive processes of cancer and can prevent metastasis. The structural base of several metal compounds shows great anticancer potential by inhibiting the signaling pathways related to cancer progression. In this minireview, we present the advances in the field of antimetastatic effects of metallodrugs. In this review, we examine the use of metallodrugs for cancer treatment, focussing on the advances in this type of therapy and the importance of these compounds, with emphasis on Pt, Ru, Au, Zn, and Cu as antimetastatic agents. In addition, we discuss the different mechanisms of action by which metallodrugs exert their therapeutic effects.