## 6 The Therapeutic Potential of Ap4A  
As outlined in the updated framework of cancer hallmarks, the functional pleiotropy of Ap4A extends to critical processes such as immune evasion and stress tolerance, reinforcing its potential as a multifaceted therapeutic target [90]. Diadenosine tetraphosphate has emerged as a multifaceted signaling molecule whose biological functions span from cell proliferation to immune modulation and metabolic adaptation. Its widespread influence appears to be largely mediated through interactions with purinergic receptors--particularly the ionotropic P2X7 receptor, which plays a central role in orchestrating many downstream effects observed across different tissues and pathological contexts. As an alarmome, Ap4A signals cellular distress and can initiate immune responses, enhancing innate immunity in the context of infections and malignancies. Importantly, the mechanisms governing Ap4A synthesis and degradation are not uniform across tissues; instead, they are highly context-dependent, shaped by each tissue's physiological demands and metabolic status. In cancer and immune cells, Ap4A regulation is particularly distinct, involving upregulated synthesis or altered degradation pathways--an aspect that offers unique opportunities for targeted therapeutic intervention, especially given the frequent dysregulation of Ap4A homeostasis in tumors. As previously discussed, the link between Ap4A, P2X7, and cancer progression is compelling. Its capacity to modulate extracellular ATP signaling--possibly by influencing ATP release or degradation--may indirectly affect P2X7 receptor activity and downstream effects within the tumor microenvironment (TME) [44]. Moreover, P2X7 not only confers survival advantages to cancer cells but also contributes to tumor angiogenesis. Among P2X receptors, P2X7 uniquely promotes the secretion of vascular endothelial growth factor (VEGF)--a critical driver of neovascularization. VEGF release has been confirmed in several cancer cell lines and other cell types such as monocytes and HEK293 cells expressing P2X7 [91]. Given its dual function in metabolic adaptation and angiogenesis, P2X7 represents a promising therapeutic target in oncology. Thus, inhibitors of P2X7 or strategies aimed at disrupting Ap4A-mediated signaling may hold potential for controlling tumor progression, immune suppression, and therapeutic resistance by modulating purinergic signaling dynamics within the TME. Moreover, Ap4A plays a role in angiogenesis by acting as an agonist at P2X1 and P2X4 receptors, stimulating endothelial cell proliferation and migration--key events in neovascularization [43; 92]. Beyond immune modulation, Ap4A analogs may also enhance immunotherapies or vaccine efficacy, particularly in immunocompromised patients. As tumors rely on neovascularization for growth and nutrient supply, targeting Ap4A-related pathways may offer novel anti-angiogenic strategies. Indeed, clinical investigations have already established P2X receptor antagonists as potential treatments for chronic cough and cancer-related pain, providing a foundation for further exploration of their application in managing other cancer-associated symptoms [42]. Recent studies have also synthesized Ap4A analogs with dual inhibitory activity at P2Y1 and P2Y12 receptors, demonstrating synergistic inhibition of platelet aggregation and underscoring Ap4A's potential as an antithrombotic agent [93]. These inhibitory properties make also Ap4A analogs attractive candidates for drug development in cardiovascular medicine. In ophthalmology, Ap4A has shown efficacy in reducing intraocular pressure (IOP) in glaucoma models, potentially through activation of P2Y6 receptors in the ciliary body, highlighting another therapeutic dimension [53]. Interestingly, Ap4A levels exhibit marked fluctuations depending on the cellular environment. Under growth-inhibitory conditions, such as amino acid starvation or serum deprivation, Ap4A concentrations drop significantly--while ATP remains relatively stable.