Targeting the Warburg effect in hematological malignancies: from PET to therapy.
OBJECTIVE
To highlight key studies providing rationale for and utility in targeting glycolysis for the treatment of hematological malignancies.


RESULTS
Several therapeutic strategies are capitalizing on the diagnostic utility of 18fluoro-deoxyglucose positron emission tomography that relies on increased glycolysis and glucose utilization in tumor cells. Although aerobic glycolysis was initially proposed by Warburg to be due to mitochondrial impairment, recent studies have shown a preferential switch to glycolysis in tumor cells with functional mitochondria. Increased glucose consumption can be advantageous for a tumor cell through stimulation of cellular biosynthetic, energetic, and pro-survival pathways. We now have a greater appreciation for the utilization of glucose in specific metabolic pathways that in some aspects can be complemented with other nutrients such as glutamine. Targeting glucose consumption for the treatment of hematological malignancies seems to be a promising field that will require characterization of tumor cell specific targets to inhibit glucose uptake and/or glycolysis. It is imperative to further our understanding of the tumor cell metabolome to target cellular bioenergetics in the treatment of cancer.


CONCLUSIONS
Targeting the glycolytic pathway for the treatment of hematological malignancies has sufficient rationale given the utility of fluoro-deoxyglucose positron emission tomography in diagnostic imaging. Further research is required in developing tumor cell specific therapeutics.
Shanmugam
Mala
M
Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois, USA. mala@northwestern.edu
McBrayer
Samuel K
SK
Rosen
Steven T
ST
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects*; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008954:Models, Biological; D010101:Oxygen Consumption / Q000187:drug effects; D049268:Positron-Emission Tomography / Q000379:methods
D000970:Antineoplastic Agents; D005947:Glucose