Linalool in cancer pharmacology: pharmacokinetic limitations and preclinical cytotoxic evidence for translational development

Cancer pharmacology increasingly evaluates plant-derived metabolites as lead compounds, but preclinical cytotoxicity should not be equated with clinical anticancer efficacy. Linalool, an acyclic monoterpene alcohol present in several aromatic plants and essential oils, has been investigated as an isolated compound and as a component of linalool-containing preparations. This critical narrative review evaluates pharmacokinetic evidence related to linalool, delivery considerations, the relevance of extraction methods, and preclinical cancer-model findings, with explicit separation of computational predictions, in vitro assays, animal studies, and human pharmacokinetic and safety evidence. Available primary evidence mainly supports cytotoxic, antiproliferative, pro-apoptotic, anti-inflammatory, and redox-modulating effects in cancer cell models, with limited evidence from animal studies and no established clinical anticancer efficacy. Reported endpoints include reactive oxygen species modulation, mitochondrial dysfunction, caspase activation, cell-cycle arrest, and changes in MAPK/ERK, PI3K/AKT, Ras/AKT/mTOR, JAK/STAT, NF-κB, and Bax/Bcl-2-related markers. However, many in vitro studies use high micromolar or millimolar concentrations that may exceed systemic exposures achievable after oral administration. Translational development therefore requires chemically standardized preparations, molar dose reporting, exposure-response validation, appropriate positive and negative controls, reproducible animal studies, and clinical studies focused initially on safety, pharmacokinetics, and realistic therapeutic endpoints.