GGCT (gamma-glutamylcyclotransferase) catalyzes the formation of 5-oxoproline from gamma-glutamyl dipeptides and plays a significant role in glutathione homeostasis. The enzyme also induces cytochrome c release from mitochondria, triggering apoptosis. In cancer contexts, GGCT is frequently upregulated across multiple tumor types including gastric cancer, papillary thyroid cancer, pancreatic ductal adenocarcinoma, and osteosarcoma, where it promotes cell proliferation and migration. GGCT exerts oncogenic effects through multiple mechanisms: it regulates the STAT3-c-Met-MEK-ERK signaling pathway 1, modulates HIF-1α expression to trigger aerobic glycolysis 2, and stabilizes CD44 to promote epithelial-mesenchymal transition 3. In papillary thyroid cancer, GGCT suppresses ferroptosis by promoting RPS15A stability and inhibiting p53-mediated SLC7A11 downregulation 4. Clinically, recent evidence suggests that GGCT inhibition offers dual benefits: in pancreatic ductal adenocarcinoma, GGCT downregulation suppresses tumor proliferation and may enhance immunotherapy responsiveness 5. Additionally, 5-oxoproline supplementation—which functions by inhibiting GGCT upstream activity—mitigates doxorubicin-induced cardiotoxicity while simultaneously suppressing tumor growth 6, positioning GGCT inhibitors and 5-oxoproline as potential therapeutic strategies.