1,8-cineole as a multi-target anticancer candidate integrating molecular mechanisms, pharmacokinetics and...

Despite decades of therapeutic innovation, cancer mortality remains largely determined by treatment resistance, systemic toxicity, and tumor heterogeneity. These persistent challenges have renewed interest in natural small molecules with multitarget activity and favorable safety profiles as adjuncts or alternatives to conventional therapies. Among these, 1,8-cineole, a monoterpene abundant in Eucalyptus and Rosmarinus species, is increasingly recognized as a promising, yet underexplored anticancer candidate. Accumulating evidence indicates that 1,8-cineole exerts broad antitumor effects. It modulates tumor cell survival, proliferation, and tumor microenvironment dynamics through multiple oncogenic signaling pathways. However, current evidence is largely limited to in vitro and early preclinical models. Tumor-specific pharmacokinetic data and clinical validation are lacking, representing major barriers to translation. Recent formulation advances, including lipid-based and nanocarrier delivery systems, have improved its stability and systemic exposure, yet tumor-targeting efficacy and pharmacokinetic-pharmacodynamic correlations remain to be established. Amid a growing yet fragmented body of preclinical research, this review integrates the current evidence on 1,8-cineole's pharmacokinetic characteristics, molecular mechanisms, and tumor-type-specific activities. Collectively, 1,8-cineole emerges as a low-toxicity, multitarget modulator that bridges natural-product pharmacology and translational oncology, warranting continued exploration to define its translational relevance. Looking ahead, standardized pharmacological assessment, rational formulation design, and multi-omics-guided strategies will be pivotal to realize its potential as a next-generation anticancer agent.