2-Deoxyglucose (2-DG) for Stage IV Cancer
Also known as: 2-DG, 2-Deoxy-D-glucose
A glucose analog that exploits the Warburg effect by competitively inhibiting glycolysis in glucose-dependent cancer cells.
Mechanism of Action
2-DG is taken up by glucose transporters and phosphorylated by hexokinase to 2-DG-6-phosphate, which cannot be further metabolized. This traps the compound intracellularly, competitively inhibiting glycolysis and depleting ATP in glycolysis-dependent cancer cells. It also induces ER stress through inhibition of N-linked glycosylation.
General mechanism: Glycolysis inhibitor. Competitive glucose analog that depletes ATP in Warburg-dependent cancer cells.
Current Evidence
Phase I/II trials show safety and tolerability. Synergistic effects with radiation therapy demonstrated in glioblastoma trials. Combination with ketogenic diet is being explored for enhanced metabolic targeting.
Clinical Status: Phase I/II trials. Emergency use authorization in India for COVID-19 (2021). Cancer trials ongoing.
Safety Profile
Hypoglycemia-like symptoms at high doses. Fatigue and sweating. Generally well-tolerated at therapeutic doses in trials.
Key Research Questions
- What is the optimal combination of 2-DG with ketogenic diet for metabolic cancer therapy?
- Can 2-DG sensitize tumors to checkpoint inhibitor therapy?
- Which metabolic subtypes of cancer are most vulnerable to glycolysis inhibition?