Herb-drug interactions in oncology: pharmacodynamic/pharmacokinetic mechanisms and risk prediction

The prevalence of herbal medicines has gained widespread, particularly among cancer patients seeking adjunctive therapies. Co-administered with anticancer drugs (ACDs) frequently, herbal medicines result in increasing cases of herb-drug interactions (HDIs), following the serious clinical consequences. While herbal medicines pose negative impacts, such as limiting efficacy and increasing toxicity of ACDs, they also offer potential benefits, including enhancing bioavailability, reducing adverse reactions, and reversing tumor drug resistance. This review is the first to systematically characterize HDI molecular mechanisms at both pharmacodynamic (PD) and pharmacokinetic (PK) levels, elucidating how herbal medicines modulate ACDs efficacy and safety through antagonism/synergy/detoxification target, metabolic enzymes, and transporters. In particular, emerging risk prediction methodologies are proposed to assess the clinical occurrence of potential PD/PK-mediated HDIs. We provide a novel insight for promoting the mechanism study of HDIs, facilitating the safe and effective integration of herbal medicines into cancer treatment.