Copper is an essential micronutrient in the human body, mainly acting as a crucial cofactor required for a wide range of physiological processes across nearly all cell types. Recent advances revealed that tumor cells seize copper to fulfill their rapid proliferation, metastasis, immune evasion, and so on by reprogramming the copper regulatory network, defined as cuproplasia. Thus, targeting copper chelation to reduce copper levels has been considered a rational tumor therapy strategy. However, overloaded copper ions could be toxic, which leads to the aggregation of lipoylated mitochondrial proteins and the depletion of iron-sulfur clusters, ultimately resulting in cell death, termed cuproptosis. Upon its discovery, cuproptosis has attracted great interest from oncologists, and targeting cuproptosis by copper ionophores exhibits as a potential anti-tumor therapy. In this review, we present the underlying mechanisms involved in cuproplasia and cuproptosis. Additionally, we sum up the chemicals targeting either cuproplasia or cuproptosis for cancer therapy. Further attention should be paid to distinguishing cancer patients who are suitable for targeting cuproplasia or cuproptosis.

Despite significant advancements in cancer treatment, current therapies often fail to completely eradicate malignant cells. This shortfall underscores the urgent need to explore alternative approaches such as cancer vaccines. Leveraging the immune system's natural ability to target and kill cancer cells holds great therapeutic potential. However, the development of cancer vaccines is hindered by several challenges, including low stability, inadequate immune response activation, and the immunosuppressive tumor microenvironment, which limit their efficacy. Recent progress in various fields, such as click chemistry, nanotechnology, exosome engineering, and neoantigen design, offer innovative solutions to these challenges. These achievements have led to the emergence of smart vaccine platforms (SVPs), which integrate protective carriers for messenger ribonucleic acid (mRNA) with functionalization strategies to optimize targeted delivery. Click chemistry further enhances SVP performance by improving the encapsulation of mRNA antigens and facilitating their precise delivery to target cells. This review highlights the latest developments in SVP technologies for cancer therapy, exploring both their opportunities and challenges in advancing these transformative approaches.

Copper, one of the essential nutrients for the human body, acts as an electron relay in multiple pathways due to its redox properties. Both deficiencies and excesses of copper lead to cellular fragility. Therefore, it can manifest pro- and anti-cancer properties in tumors. Therefore, it is crucial to clarify the copper activity within the cell. We have thoughtfully summarized the metabolic activities of copper from a macro and micro perspective. Cuproptosis, as well as other forms of cell death, is directly or indirectly interfered with by Cu²⁺, causing cancer cell death. Meanwhile, we did pan-cancer analysis of cuproptosis-related genes to further clarify the roles of these genes. In addition, copper has been found to be involved in multiple pathways within the metastasis of cancer cells. Given the complexity of copper's role, we are compelled to ask: is copper a friend or a foe? Up to now, copper has been used in various clinical applications, including protocols for measurement of copper concentration and bioimaging of radioactive ⁶⁴Cu. But therapeutically it is still a continuation of the old medicine, and new possibilities need to be explored, such as the use of nanomaterials. Some studies have also shown that copper has considerable interventional power in metabolic cancers, which provides the great applications potential of copper therapy in specific cancer types. This paper reviews the dual roles played by cuproptosis in cancer from the new perspectives of oxidative stress, cell death, and tumor metastasis, and points out the value of its application in specific cancer types, summarizes the value of its testing and imaging from the perspective of clinical application as well as the current feasible options for the new use of the old drugs, and emphasizes the prospects for the application of nano-copper.

Background: Helicobacter pylori (H. pylori) infection contributes significantly to gastric cancer (GC) progression. The intrinsic mechanisms of H. pylori-host interactions and their role in promoting GC progression need further investigation. In this study, we explored the potential role of fat mass and obesity-associated protein (FTO) in mediating Cytotoxin-associated gene A (CagA)-induced GC progression.

Methods: The effects of H. pylori infection on N⁶-methyladenosine (m⁶A) modification were evaluated in both human samples and GC cell lines. The function of FTO in the progression of GC was elucidated through in vitro and in vivo studies. A series of techniques, including methylated RNA immunoprecipitation sequencing, RNA sequencing, RNA binding protein immunoprecipitation, and chromatin immunoprecipitation assays, were utilized to investigate the mechanism by which FTO mediates the capacity of cagA-positive H. pylori to promote GC progression. Furthermore, the therapeutic potential of the FTO inhibitor meclofenamic acid (MA) in impeding GC progression was evaluated across GC cells, animal models, and human GC organoids.

Results: Infection with cagA-positive H. pylori upregulated the expression of FTO, which was essential for CagA-mediated GC metastasis and significantly associated with a poor prognosis in GC patients. Mechanistically, CagA delivered by H. pylori enhanced FTO transcription via Jun proto-oncogene. Elevated FTO induced demethylation of m⁶A and inhibited the degradation of heparin-binding EGF-like growth factor (HBEGF), thereby facilitating the epithelial-mesenchymal transition (EMT) process in GC cells. Interestingly, eradication of H. pylori did not fully reverse the increases in FTO and HBEGF levels induced by cagA-positive H. pylori. However, treatment with a combination of antibiotics and MA substantially inhibited cagA-positive H. pylori-induced EMT and prevented GC metastasis.

Conclusion: Our study revealed that FTO mediates the “hit-and-run” mechanism of CagA-induced GC progression, which suggests that the therapeutic targeting of FTO could offer a promising approach to the prevention of CagA-induced cancer progression.