Glycyrrhetinic Acid in Cancer Therapy: Mechanistic Insights, Therapeutic Potential, and Future Directions

Cancer presents a significant and growing global health challenge in the 21st century, marked by a rising number of new diagnoses and cancer-related deaths reported annually. Glycyrrhetinic Acid (GA), a triterpenoid compound derived from the licorice plant, Glycyrrhiza glabra, G. inflata, and G. uralensis, has a long-standing history of use in traditional healing practices. In this comprehensive review, the evolving research on GA's pharmacological properties published between 2015 and 2024, with a specific focus on its potential as a cancer therapy, is critically analyzed. In preclinical studies, GA showed anti-tumor effects and modulated several cellular pathways involved in cancer growth. Despite this promising anti-tumor activity, GA's clinical use is still being evaluated because of poor solubility and low bioavailability. A clear understanding of GA's complex pharmacokinetics is necessary to optimize its clinical application. This work explores how GA may act against cancer, including its capacity to enhance chemotherapeutic treatments and its interactions in the tumor microenvironment. In addition, this paper critically reviews GA's therapeutic potential across different cancer types and discusses new formulation approaches, pointing to key directions for future clinical and translational studies. This review summarizes the existing evidence on GA and discusses its potential use as a treatment in oncology. Further research is needed to assess GA's effectiveness and safety in clinical studies. Such investigations can help translate laboratory results into practical use in clinical settings.