TARGETED CANCER THERAPY VIA PURINERGIC RECEPTOR INHIBITION: THE USE OF P2X7 ANTAGONISTS

Abstract

The purinergic P2X7 receptor (P2X7R), a member of the ATP-gated ion channel family, has emerged as a crucial player in cancer pathophysiology, including tumor growth, inflammation, and immune evasion. Overexpression of P2X7R has been reported in several aggressive malignancies, including breast cancer, pancreatic ductal adenocarcinoma, and glioblastoma, correlating with poor prognosis and treatment resistance. Targeting P2X7R through selective antagonists has thus gained considerable attention as a novel therapeutic strategy. This study explores the potential of P2X7R antagonists as targeted agents in oncology by evaluating their molecular mechanisms, expression profiles in various cancers, and preclinical efficacy. We present a comparative analysis of known P2X7R inhibitors, including A-740003, Brilliant Blue G, KN-62, AZ10606120, and oxidized ATP, highlighting their pharmacodynamics and antitumor activities. In vitro and in vivo experiments demonstrate that blockade of P2X7R results in reduced proliferation, migration, and enhanced apoptosis in cancer cells. The inhibitory effects are particularly notable in models of breast and pancreatic cancer, suggesting receptor-specific therapeutic vulnerabilities. Our findings support further development of P2X7R antagonists as adjuncts or alternatives to conventional therapies. These insights may pave the way for novel, receptor-specific cancer treatments with higher efficacy and lower systemic toxicity.