Unlocking the anticancer code of gambogic acid: Multidimensional strategies to overcome tumor treatment challenges

Gambogic acid (GA), a natural xanthonoid derived from Garcinea hanburyi, demonstrates potent multi-targeted anticancer activity through induction of apoptosis, autophagy, and cell cycle arrest, while concurrently inhibiting tumor invasion, metastasis, and angiogenesis. However, its clinical translation is impeded by poor aqueous solubility, low bioavailability, rapid metabolism, and potential toxicity. This review synthesizes key advancements aimed at overcoming these limitations: A bibliometric analysis (2001-2024) quantitatively delineates the evolving research landscape, identifying leading institutions, high-impact journals, and emerging foci such as nanotechnology-enabled delivery. We critically evaluate innovative strategies, including structural modification to optimize pharmacokinetics, stimulus-responsive prodrug design, novel nano-delivery systems (passively and actively targeted), and synergistic combination therapies (e.g., with chemotherapy, photothermal, or photodynamic modalities). By integrating these approaches, this review proposes an integrated roadmap to advance GA from preclinical promise to clinical viability, with significant implications for oncology and nanomedicine.