Cell metabolism has been called the "Achilles Heel" of cancer, an opportunity to attack tumors as they consume essential nutrients to feed their hyperproliferative nature. However, many of the experiments exploring how cancer cells metabolize these nutrients are conducted in plastic dishes, several steps removed from an in vivo environment.
To more faithfully model these processes, researchers in the KI's Vander Heiden lab infused tumor-bearing mice with isotope-labeled glucose and glutamine (two important molecules for fueling cancer cell replication and proliferation) and compared their fates in both tumor and normal tissue. In both situations, glucose was converted to lactate at an expectedly elevated rate (cancerous cells are commonly observed to increase lactate production) but the cells' utilization of glutamine did not increase, a starkly different result than that observed in analogous experiments performed in tissue culture.
The conclusion that in vitro results cannot be applied uniformly to in vivo environments is not unexpected, but it is indicative of the importance of understanding the context in which metabolic processes occur. Using in vivo metabolic tracking presents an exciting opportunity for probing the metabolic properties of multiple tumor types in vivo, and can lead to novel insights into the biology of human cancers. Mouse models that faithfully recapitulate human cancers will be critical for identifying tumors' vulnerabilities within a given tissue and give researchers a "heel" up on designing therapies that target cancer metabolism