The Endocannabinoid System in Cancer Biology: A Mini-Review of Mechanisms and Therapeutic Potential

Kaio Cezar Rodrigues Salum^1*Gabriel Brendo Alves Miranda²Alessandra Lima Dias²JOÃO REGIS IVAR CARNEIRO¹Patricia Bozza³Ana Carolina Proença Da Fonseca^3*Tamara Silva²

• ¹Clementino Fraga Filho University Hospital, Center for Health Science, Federal University of Rio de Janeiro, Rio de Janeiro, Paraná, Brazil
• ²Genetics Laboratory, Grande Rio University/AFYA, Rio de Janeiro, Paraná, Brazil
• ³Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil

The Endocannabinoid System (ECS) plays a critical role in maintaining physiological homeostasis, influencing a range of processes such as neuroprotection, inflammation, energy metabolism, and immune responses. Comprising cannabinoid receptors (CB1 and CB2), endogenous ligands (endocannabinoids), and the enzymes responsible for their synthesis and degradation, the ECS has attracted increasing attention in cancer research. Cannabinoid receptor activation has been associated with the regulation of cancer-related processes, including cell proliferation, apoptosis, and angiogenesis, suggesting that the ECS may have a role in tumor progression and cancer treatment. Preclinical studies have shown that cannabinoids, through their interaction with CB1 and CB2 receptors, can inhibit tumor cell growth, induce programmed cell death, and suppress the formation of new blood vessels in various cancer models. Despite these encouraging findings, the clinical translation of ECS-targeted therapies remains in its early stages. The complexity of tumor heterogeneity, the variability in patient responses, and the challenges associated with the pharmacokinetics of cannabinoids are significant obstacles to the broader application of these findings in clinical settings. This review provides an overview of the current understanding of the ECS's involvement in cancer biology, focusing on key mechanisms by which it may influence carcinogenesis. Additionally, we discuss the therapeutic potential of targeting the ECS in cancer treatment, while highlighting the limitations and uncertainties that need to be addressed through ongoing research.