Advances and challenges in betulinic acid therapeutics and delivery systems for breast cancer prevention and treatment

Breast cancer (BC) is the leading cause of cancer-related death among women worldwide. Due to limited treatment options for patients with advanced BC, preventive and innovative therapeutic strategies are essential to combat this disease. Therefore, finding safe and effective anticancer treatments remains a significant challenge in the 21st century. Plant-derived triterpenoids, widely used for medicinal purposes, exhibit various biological activities. Most triterpenoids are cytotoxic to multiple tumor cells and demonstrate anticancer effects in preclinical animal models. One example is betulinic acid (BA), a natural product mainly extracted from the bark of birch trees. BA is a promising anti-tumor compound with numerous pharmacological properties. However, its poor water solubility limits its optimal therapeutic potential. Additionally, the low BA content in plants hampers large-scale production from these sources. To address these issues, extensive research has focused on producing BA through chemical synthesis and biotransformation. Furthermore, several BA derivatives have been developed through structural modifications, and various delivery systems have been created to improve solubility and enhance therapeutic efficacy. This review discusses recent advances and challenges related to BA and its derivatives in preventing and treating breast tumors, as well as the potential obstacles and future directions for improving delivery systems in BC therapy.