Copper homeostasis as target of both consolidated and innovative strategies of anti-tumor therapy

Background: Copper was reported to be involved in the onset and progression of cancer. Proteins in charge of copper uptake and distribution, as well as cuproenzymes, are altered in cancer. More recently, proteins involved in signaling cascades, regulating cell proliferation, and anti-apoptotic protein factors were found to interact with copper. Therefore, therapeutic strategies using copper complexing molecules have been proposed for cancer therapy and used in clinical trials. Objectives: This review will focus on novel findings about the involvement of copper and cupro-proteins in cancer dissemination process, epithelium to mesenchymal transition and vascularization. Particularly, implication of well-established (e.g. lysil oxidase) or newly identified copper-binding proteins (e.g. MEMO1), as well as their interplay, will be discussed. Moreover, we will describe recently synthesized copper complexes, including plant-derived ones, and their efficacy in contrasting cancer development. Conclusions: The research on the involvement of copper in cancer is still an open field. Further investigation is required to unveil the mechanisms involved in copper delivery to the novel copper-binding proteins, which may identify other possible gene and protein targets for cancer therapy.