Vascular Dysfunction-Driven Lipid Mislocalization and FFA-Linked Injury in Solid Tumors: A Mechanistic Review

Abnormal tumor vasculature, hypoxia, altered lipid use, oxidative-matrix injury, and immune remodeling often coexist, but their spatial and causal relationships remain incompletely resolved. We examine whether vascular boundary failure can pathologically relocate circulating apolipoprotein B (ApoB)-containing triglyceride-rich lipoproteins (ApoB-TRLs) into the tumor interstitium and thereby create a focal source of free fatty acid (FFA)-linked injury.

We conducted a structured narrative review of literature identified through PubMed and reference-chain searches through 8 August 2026. Evidence was appraised according to tumor specificity, compartmental directness, spatiotemporal resolution, and perturbation consistency.

Current evidence directly supports abnormal tumor vascular permeability and hypoxia-VEGF coupling, whereas evidence from tumor and adjacent fields provides context-dependent support for the interstitial access and local processing of circulating ApoB-containing particles, FFA-linked oxidative and inflammatory injury, and macrophage lipid remodeling. The evidence does not yet establish in one spatially and temporally resolved tumor model that pathological extracellular ApoB-TRL/TG mislocalization generates a defined injury field and increases later particle entry. Tumor-associated Lipid Pathologic Resonance (tumor-LPR) is therefore retained as a bounded subset hypothesis organized around three domains: pathological spatial mislocalization, FFA-injury coupling, and feedback closure.

Tumor-LPR is not generic permeability, hypoxia, or intracellular lipid storage. The framework provides testable intervention logic and explicit falsifiers, but it is not a universal tumor mechanism or a clinical treatment algorithm.