CURGET: a combination of common-use polyphenols plus trimetazidine as metabolic therapy for Cancer: a theoretical proposal

INTRODUCTION: Repurposing inexpensive oral compounds targeting metabolic reprogramming is a pragmatic strategy. CURGET is a five-node oral regimen designed to induce metabolic starvation in tumors. AREAS COVERED: Comprehensive literature search.The malignant phenotype features concurrent upregulation of glycolysis (HK2), glutaminolysis (GLS1), de novo lipogenesis (FASN), the mevalonate pathway (HMGR), and fatty-acid β-oxidation (FAO/3-KAT). CURGET combines four widely available polyphenols and a common cardiac drug: curcumin, urolithin A, resveratrol, EGCG, and trimetazidine to target these five enzymes. Additional mechanisms include context-dependent pro-oxidant activity and epigenetic modulation such as DNMT, HDAC, and HAT inhibition linked to cofactor depletion. This review synthesizes human safety and pharmacokinetic data, plasma AUC overlap with in vitro inhibitory concentrations, knockout evidence of metabolic plasticity, and clinical co-expression of HK2, GLS1, and FASN. EXPERT OPINION: CURGET represents a coherent, low-cost oral strategy rather than a finalized protocol. Key priorities include developing bioavailable formulations, conducting preclinical studies with defined metabolic endpoints, and early-phase pharmacokinetic and safety assessments of the combination. If CURGET shows a favorable therapeutic index, it may be most applicable to metabolically characterized tumors, including gastric, pancreatic, and selected breast cancers. Successful development could improve access to affordable metabolic adjuncts and help reduce global disparities in cancer care.