Work

Lipid Metabolic Reprogramming in Thyroid Cancer: Systemic Biomarkers, Tumor Dependencies and Therapeutic Resistance

Year: 2026

Type: review

Abstract: Lipid metabolic reprogramming is increasingly implicated in thyroid cancer progression and treatment resistance alongside circulating lipid associations are often conflated with tumor lipid dependency. A clinically useful synthesis must distinguish systemic lipid markers from intratumoral lipid flux before integrating them into mechanistic or therapeutic models. This critical narrative review integrates evidence across three connected layers: circulating lipid markers; tumor-intrinsic uptake, oxidation, synthesis, desaturation, cholesterol and oxysterol pathways; and immune-spatial niches involving macrophage lipid handling, APOE-associated polarization and ferroptosis-related lipid peroxidation. In papillary thyroid carcinoma, multi-omics and mechanistic studies implicate LPL-FATP2-CPT1A, PC-AKT/mTOR-SREBP1c-FASN and METTL16/YTHDC2/SCD1 programs in membrane remodeling, invasion-related behavior and recurrence risk stratification. In aggressive and anaplastic thyroid cancer, cholesterol synthesis signaling, fatty acid oxidation adaptation and SREBF1/SCD1-linked ferroptosis defense may contribute to resistance to radioiodine, radiotherapy, chemotherapy and BRAF/MEK inhibition. The current evidence is strongest for mechanistic and biomarker hypotheses; thyroid-cancer-specific prospective trials of lipid-directed treatment are lacking. Lipid metabolism therefore provides a framework for molecular stratification and treatment sensitization, but it does not currently justify nonspecific lipid lowering or routine lipid-targeted therapy. Translation will require paired blood and tumor lipidomics, spatial profiling, functional perturbation and biomarker-defined prospective studies.

Source: Metabolites

DOI: 10.3390/metabo16100736