Bioactive plant and fungal metabolites in oral cancer: molecular mechanisms and translational potential

assays. Pharmacokinetic bridging, toxicity evaluation, and clinically relevant validation are still limited. Importantly, several polyphenolic metabolites exhibit pan-assay interference (PAINS) liabilities, requiring cautious interpretation of pathway-level findings. Advances in nano-delivery systems, rational structural optimization, and combination strategies may improve exposure and selectivity. Future work should emphasize PAINS-aware pharmacological rigor, orthogonal target validation, advanced translational models, and biomarker-driven clinical trials to support the development of genuinely druggable natural metabolite candidates for oral cancer management.