Cannabinoid Receptor 2 in Cancer: A Mini-Review of Expression, Prognosis,and Molecular Mechanisms of Action

Introduction: The cannabinoid receptor 2 (CB2), part of the endocannabinoid system, is a key regulator of immune function whose peripheral expression makes it an attractive therapeutic target in oncology, avoiding the psychoactive effects of the CB1 receptor. Methods: This mini-review comprehensively summarizes the current understanding of the CB2 receptor's multifaceted role in cancer, integrating preclinical studies with bioinformatics network validation. Results: Literature synthesis reveals that CB2 expression and prognostic value are highly context- dependent, correlating with improved survival in hepatocellular carcinoma but poor prognosis in HER2+ breast cancer. Network analysis confirms the CNR2 gene as a central hub suppressing the PI3K/AKT/mTOR axis and interacting with CXCR4 and TLR4. Discussion: The contradictory roles of CB2 across malignancies, such as immunosuppression in NSCLC versus protective immune roles in melanoma, highlight the importance of the tumor microenvironment (TME). Conclusion: The CB2 receptor is a promising pharmacological target in oncology. However, its complex, context-dependent effects underscore the need for further research, informed by system- level bioinformatics, to fully understand its cell-specific functions and develop tailored, effective anti-cancer therapies.