Relationship between purinergic signalling and oxidative stress in prostate cancer: Perspectives for future therapy

Abstract

Prostate cancer (PCa) is a complex and lethal disease in men, influenced by risk factors such as age, heredity, and lifestyle. This article reviews the roles of purinergic signaling and reactive species in PCa progression. The purinergic system involves signaling molecules, such as ATP and adenosine, specific receptors (P1 and P2), and catalytic enzymes (for example, CD39 and CD73), whose alterations contribute to cell proliferation, angiogenesis, and immune evasion. The purinergic receptors P2X7 and P2X4 modulate the prostate tumor microenvironment (TME), impacting hypoxia, apoptosis, and inflammatory pathways. Reactive oxygen species (ROS) and nitrogen species (RNS) also play crucial roles. At elevated levels, they lead to oxidative damage to DNA and mitochondria, promoting genetic instability and uncontrolled cell proliferation. These species interact with the purinergic signaling pathway, with enzymes like CD39 and CD73 playing dual roles: degrading extracellular ATP to generate immunosuppressive adenosine while simultaneously protecting against oxidative damage. This review emphasizes the dynamic interplay between inflammatory and immunosuppressive signals within the TME, mediated by ATP, ROS, and their signaling cascades. This balance determines whether the environment supports tumor progression or regression. Targeting these mechanisms through innovative therapies, including receptor inhibitors and ROS modulation, presents promising avenues for PCa treatment. Understanding the intricate roles of purinergic signaling and reactive species provides valuable insights into potential therapeutic strategies to combat PCa.