Hexokinase 2 required in tumors

It is well known that cancer cells have elevated glucose metabolism, and much effort has been directed at identifying targets that will selectively disrupt this pathway in cancer. Hexokinases catalyze the first committed step in glucose metabolism and are highly expressed in cancer cells. Using Hk2 conditional knockout mice, Nissim Hay and colleagues show that hexokinase 2 is required for tumor initiation and maintenance in mouse models of cancer (Cancer Cell doi:10.1016/j.ccr.2013.06.014, 1 August 2013). The authors crossed mice carrying activated KRas (Kras^LSL-G12D), a model of non–small-cell lung cancer, or mice carrying activated ErbB2 (Neu), a model of breast cancer, to Hk2 conditional knockout mice. They found that the average tumor size in Kras^LSL-G12D; Hk2^−/− mice was significantly smaller than in Kras^LSL-G12D; Hk2^fl/fl undeleted controls. They also found that mortality was profoundly delayed in the mice with activated KRas and Hk2^−/−. Loss of Hk2 had a similar effect in ErbB2-driven mammary gland tumorigenesis, as Hk2 deletion slowed the onset of tumors and reduced their incidence. Small-molecule inhibitors of HK2 may be a therapeutic approach in cancer, although the authors note that it may be challenging to develop specific inhibitors to HK2 that do not affect the closely related HK1 protein.