Colchicine, a classical microtubule-targeting agent (MTA), exhibits remarkable anti-tumor potential, but its clinical translation is severely restricted by a narrow therapeutic window, systemic off-target toxicity, and complex pharmacokinetic vulnerabilities. Driven by the objective of “toxicity reduction and efficacy enhancement,” this review comprehensively summarizes colchicine’s multidimensional translational research. First, precise chemical modifications of its tricyclic scaffold and multi-site synergistic strategies are analyzed, exploring structure-activity relationship (SAR) mechanisms in enhancing target affinity and reversing multidrug resistance (MDR). Second, precision delivery systems—including prodrug-anchored liposomes, stimuli-responsive smart nanocarriers, inorganic mesoporous platforms, and photodynamic co-delivery—are evaluated, demonstrating their capacity to overcome biophysical barriers, reshape spatiotemporal distribution, and mediate immune synergy. Furthermore, the risks of drug-drug interactions (DDIs) and pharmacodynamic synergy arising from colchicine’s cytochrome P450 3A4 (CYP3A4)/P-glycoprotein (P-gp) dual-substrate nature in complex oncology regimens are dissected. To address this, a clinical management framework integrating ultrasensitive trace sensing and macroscopic pharmacovigilance is proposed. Finally, current translational gaps are critically confronted, notably the over-reliance on the enhanced permeability and retention (EPR) effect and the in vitro - in vivo druggability disconnect. Breakthrough paradigms like targeted protein degradation (TPD, e.g., PROTACs) and dynamic responsive carriers are subsequently proposed to guide the future precision clinical innovation of colchicine therapeutics.
Jin et al. (Fri,) studied this question.