Methods of reducing expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) and methods of treating a cancer in a cell are provided, the methods including contacting a cell with an effective amount of a PFKFB4 inhibitor. Short hairpin RNA (shRNA) and small interfering RNA (siRNA) inhibitors of PFKFB4 and their methods of use are also provided.