Emerging Coumestans in Cancer Therapy With Mechanistic Insights and Clinical Potential

Coumestans are natural phytoestrogens with strong therapeutic potential for inhibiting hormone-induced cancers, such as breast, ovarian, and prostate malignancies. They regulate many signaling pathways, including the PI3K/AKT, MAPK, NF-κB, and JAK/STAT pathways. Challenges regarding the clinical application of coumestans include their poor bioavailability and distribution, rapid metabolic rate, low water solubility, and formulation. This review aims to provide a comprehensive overview of the anticancer mechanisms of a few important coumestan derivatives, namely coumestrol, wedelolactone, isofraxidin, and psoralidin. Methods for increasing the coumestan efficacy via synthetic biology, bioinformatics, and artificial intelligence are described in this review. To bridge the gap between bench to bedside, future directions should focus on emphasizing clinical validation and developing targeted delivery systems to understand the therapeutic potential of coumestans.