Unleashing the Therapeutic Power of Natural Alkaloids in Triple-Negative Breast Cancer: State-of-the-Art Advances and Future Directions.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype characterized by the absence of ER, PR, and HER2, presenting significant challenges due to its heterogeneity and limited treatment options. Recent studies have identified naturally derived alkaloids as promising therapeutic agents, capable of targeting critical signaling pathways involved in TNBC progression, including PI3K/AKT/mTOR, STAT3, TGF-β, NF-κB, and p38 MAPK. This review provides a comprehensive overview of the past decade's advancements in alkaloid-based therapies for TNBC, emphasizing their impact on key pathways. Additionally, it discusses the challenges in clinical translation, such as poor bioavailability and toxicity, and explores future directions for their application in TNBC treatments, highlighting the potential for innovative and personalized therapeutic strategies. Overall, natural alkaloids hold significant promise in the quest for innovative TNBC treatments. By selectively targeting pivotal signaling pathways, these compounds could pave the way for more personalized therapy and improved patient outcomes; further high-quality studies are essential to firmly establish their clinical efficacy.