Evolving approaches in glioma treatment: harnessing the potential of copper metabolism modulation

The key properties and high versatility of metal nanoparticles have shed new perspectives on cancer therapy, with copper nanoparticles gaining great interest because of the ability to couple the intrinsic properties of metal nanoparticles with the biological activities of copper ions in cancer cells. Copper, indeed, is a cofactor involved in different metabolic pathways of many physiological and pathological processes. Literature data report on the use of copper in preclinical protocols for cancer treatment based on chemo-, photothermal-, or copper chelating-therapies. Copper nanoparticles exhibit anticancer activity via multiple routes, mainly involving the targeting of mitochondria, the modulation of oxidative stress, the induction of apoptosis and autophagy, and the modulation of immune response. Moreover, compared to other metal nanoparticles (e.g. gold, silver, palladium, and platinum), copper nanoparticles are rapidly cleared from organs with low systemic toxicity and benefit from the copper's low cost and wide availability. Within this review, we aim to explore the impact of copper in cancer research, focusing on glioma, the most common primary brain tumour. Glioma accounts for about 80% of all malignant brain tumours and shows a poor prognosis with the five-year survival rate being less than 5%. After introducing the glioma pathogenesis and the limitation of current therapeutic strategies, we will discuss the potential impact of copper therapy and present the key results of the most relevant literature to establish a reliable foundation for future development of copper-based approaches.