LAUSR

ABSTRACT Introduction: It has been known for over half a century that tumors exhibit an increased demand for nutrients to fuel their rapid proliferation. Interest in targeting cancer metabolism to treat the disease has been renewed in recent years with the discovery that many cancer-related pathways have a profound effect on metabolism. Considering the recent increase in our understanding of cancer metabolism and the enzymes and pathways involved, the question arises as to whether metabolism is cancer’s Achilles heel. Areas covered: This review summarizes the role of 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in glycolysis, cell proliferation, and tumor growth, discussing PFKFB3 gene and isoenzyme regulation and the changes that occur in cancer and inflammatory diseases. Pharmacological options currently available for selective PFKFB3 inhibition are also reviewed. Expert opinion: PFKFB3 plays an important role in sustaining the development and progression of cancer and might represent an attractive target for therapeutic strategies. Nevertheless, clinical trials are needed to follow up on the promising results from preclinical studies with PFKFB3 inhibitors. Combination therapies with PFKFB3 inhibitors, chemotherapeutic drugs, or radiotherapy might improve the efficacy of cancer treatments targeting PFKFB3.