GLUT5 Targeted Drug Delivery in Cancer: A Critical Narrative Review of Transporter Specificity and Translational Design

Background/Objectives: GLUT5 (SLC2A5) is a fructose transporter investigated as a route for cancer drug delivery. This review examines whether the evidence supports transporter dependence, intracellular cargo delivery and therapeutic selectivity as distinct claims. Methods: Fourteen representative empirical reports were mapped using six qualitative evidence domains. Europe PMC searches of PubMed-indexed title and abstract records, updated on 16 October 2026, retrieved 53 and 98 records, with 138 unique records after deduplication. Main texts were inspected for 12 reports; one additional appraisal used a scoped accepted manuscript extraction, and one remained abstract-based. ClinicalTrials.gov searches retrieved 48 unique records. Results: GLUT5 structures support alternating access to a monosaccharide-binding cavity; passage of typical intact nanocarriers through this route is structurally implausible and unproven. Carrier studies instead show formulation-dependent cellular association, competition-sensitive uptake and, in selected systems, functional payload activity. Full-text appraisal credits the single-ligand and competition controls in dual-targeting liposomes and the competition and independent death measurements in porphyrin glycopolymers. These controls do not establish exclusive GLUT5 dependence. Target accessibility, physicochemical matching, inhibitor conditions, intracellular construct identity and genetic rescue remain recurrent limitations. No eligible GLUT5-targeted anticancer therapeutic delivery study was identified in the specified registry search. Conclusions: Fructose-associated uptake is a useful observation whose mechanism must be resolved for each construct. Genetic loss and rescue, chemical or physical confirmation of the delivered species, and efficacy linked to tolerated exposure should guide further development. The evidence map is representative rather than exhaustive, and access limits preclude absence-of-control judgments for the abstract-only report.